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Home , Acatalasia, Aldolase A, Bile acid sequestrant, Danon disease, Endothelial lipase, Essential fructosuria

Appendix A: Used in the Treatment of Inborn Errors

JH Walter and JE Wraith

J.-M. Saudubray et. al (Eds.), Inborn Metabolic Diseases, DOI 10.1007/978-3-642-15720-2, © Springer- Verlag Berlin Heidelberg 2012 626 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Agalsidase Recombinant analogue of 0.2 mg/kg alt weeks IV 40 alfa (Repla- human α-galactosidase gal) A manufactured by activation in human fibro- blast cell line

Agalsidase Recombinant analogue of Fabry disease 1.0 mg/kg alt weeks IV 40 beta (Fabra- human α-galactosidase A zyme) manufactured in Chinese Hamster Ovary (CHO) cell line

Aglucosi- Recombinant analogue Pompe disease 20 mg/kg alt weeks IV 6 dase alfa of human α-glucosidase (Myozyme®) manufactured in Chinese Hamster Ovary (CHO) cell line

AllopurinolXanthine-oxidase inhibitor Disorders leading Initial dosage 10-20 Oral36 to hyperuricaemia mg/kg per day in chil- (PRPP synthetase dren and 2-10 mg/kg superactivity; HGPRT per day in adults deficiency) and APRT deficiency

Ammonium Chelating agent Wilson’s disease 160 mg/d in 6 divided Oral38 tetrathiomo- doses lybdate

Betaine Remethylates hct to meth Classic homocysti- 100-150 mg/kg/day in Oral21 nuria two to three divided Remethylation de- doses, max. dose 6-9 fects g/d

Biotin Co-factor for carboxylases Biotinidase defi- 5-20 mg/d Oral or 27 Treatment of presumed ciency, IV 2 transporter defect Multiple carboxylase deficiency Biotin-responsive disease

Chenode- Inhibits 7a- 3β- 3β-D: 12-18 mg/kg/d Oral34 oxycholic hydroxylase (rate-limiting def (3β-D); for first 2 months then acid in acid biosyn- Δ4-3-Oxosteroid 5β- 9-12 mg/kg/d; 3-ORD thesis) reductase deficiency :8 mg/kg/day; CTX: 750 (3-ORD); Cerebroten- mg/day (adults) dinous xanthomato- sis (CTX)

CholesterolReplenishes cholesterolSmith-Lemli-Opitz 20-40 mg/kg/d in 3-4 Oral33 (SLO) syndrome divided doses

Cholesty- sequestrant Familial hypercholes- Adults: 12-24 g /d OralPossible 32 ramine terolaemia children: (wt in kg/70 A, D, x adult dose ) in four and K defi- divided doses ciency with prolonged treatment. Other bile acid resins include & colesevalam 627 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Cholic acidΔ4-3-Oxosteroid 5β- 8 mg/kg/day Oral33 reductase deficiency (3-ORD)

Copper Increases intracellular 100-200 μg Cu/d (new- SC 38 copper born) 1 mg Cu/d in older children

Creatine Replenishes Guanidinoacetate 300-400 mg/kg/d in Oral16 monohy- methyltransferase three to six divided drate (GAMT) deficiency doses : amidinotransferase (AGAT) deficiency

Cyclic pyra- Replenishes deficient prod- Molybdenum co- 80-160 mg/kg/d IV 36 nopterin uct to allow production of factor deficiency monophos- molybdenum co-factor type A phate (cPMP)

Cysteamine/ Depletes lysosomal cystine 1.3 g/m2/day of free- Oral Phospho- 43 phospho- base), given every 6 h and eye cysteamine drops more palat- able

Dextro- NMDA channel antagonist NKH 5-7 mg/kg/d in four Oral Doses up to 24 methorphan divided doses 35/mg/d have been used

Diazoxide Inhibits secretion Persistent hyperinsu- 15 mg/kg/d (newborn); Oral10 linism 10 mg/kg/d (infants), in three divided doses

Dichloroac- Stimulates PDH activity by Primary lactic aci- 50 mg/kg/d in 3-4 di- Oral May cause 12 etate inhibiting PDH dosis vided doses polyneurop- athy with prolonged use

Entacapone Prevents the peripheral Disorders of BH4 15mg/kg/d in two to Oral17 breakdown of l-dopa synthesis three divided doses

Ezetimibe Inhibits cholesterol absorp- Familial hypercholes- 10 mg/d Oral32 tion terolaemia

Folinic acidProvides accessible source DHPR deficiency, 5-15 mg/d Oral, IV 17, 28 of for CNS UMP synthase defi- ciency (hereditary ), Methylene synthase deficiency, synthase deficiency, Hereditary folate ma- labsorption, Some disorders of cobalamin metabo- lism, Cerebral folate trans- porter 628 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Galsulfase Recombinant analogue Mucopolysacchari- 1.0 mg/kg per weekIV 40 (Naglazyme) of human N-acetylga- dosis type VI lactosamine 4 manufactured in Chinese Hamster Ovary (CHO) cell line

GemfibrozilFibrates decrease TG levels; Mixed or combined Adult dose: 1.2 g daily, OralCan cause a 32 other include beza- hyperlipidaemia usually in two divided myositis-like and doses; range 0.9–1.5 g syndrome, daily especially with impaired renal function; combination with a increases risk of rhabdomy- olysis

G-CSF Stimulates granulocyte in GSD 5 μg/kg once daily SC 6 production Ib, Ic

Glycine Forms isovalerylglycine Isovaleric acidaemia 150 mg/kg/d in three OralUp to 600 mg/ 19 with high renal clearance divided doses kg/d during decompensa- tion

Haem Inhibits 5-aminolevulinic Acute porphyrias 3-4 mg/kg once daily IV 37 arginate acid synthase for 4 days

Hydroxoco- Co-factor for methylmalo- Disorders of cobala- 1 mg IM daily; oral IM or Dose may 19, 28 balamin nyl mutase min dose 10 mg once or oral be reduced

(vitamin B12) twice daily to once or twice weekly according to response

5-Hydroxy- Neurotransmitter replace- Disorders of neu- 1-2 mg/kg, increasing Oral Monitor CSF 17,29 ment rotransmitter syn- gradually to 8-10 mg/ 5HIAA levels thesis kg in 4 divided doses

Idursulfase Recombinant iduronate- MPS II 0.5 mg per kg by IV IV 40 (Elaprase®) 2-sulfatase produced in infusion weekly human cell line

Imiglucerase Recombinant Gaucher disease Various regimens: IV 40 (Cerezyme) analogue of human 2.5 U/kg 3X per week β- to manufactured in Chinese 60 U/kg per 2 weeks Hamster Ovary (CHO) line For type III Gaucher disease some clinicians recommend higher dosages: 120 U/kg per 2 weeks

Ketamine N-Methyl-d-aspartate NKH 1-30 mg/kg/d in four Oral or 24 (NDMA) channel antago- divided doses IV nist

l–Arginine Replenishes arginine; sub- disorders; 50-170 mg/kg (OCT Oral or IV loading 20 strate of nitrous oxide MELAS and CPS def) IV dose: (200 Up to 700 mg/kg in AL mg/kg) over & AS def 90 min 629 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Laronidase Recombinant ana- Mucopolysacchari- 100 U/kg per weekIV 40 (Aldura- logue of human α-l- dosis type I zyme) manufac- tured in Chinese Ham- ster Ovary (CHO) line

l- Replenishes body stores; Primary and second- 100-200 mg/kg/d Oral or Do not use ra- 13, 19, ,23 Removes toxic acyl-CoA ary carnitine defi- IV cemix mixture intermediates from within ciencies the mitochondria

l-Citrulline Replenishes citrulline and Used as an alterna- CPS & OCT def: 170 Oral 20, 26 arginine tive to arginine in mg/kg/day or 3.8 gm/ CPS def and OCT m2/day in divided dos- def; LPI es, LPI: 100 mg/kg/d in 3-5 doses

l-Dopa Replacement of neu- Disorders of l-dopa 1-2 mg/kg increasing OralGive as l-do- 17,29 rotransmitters synthesis slowly to 10-12 mg/kg pa/carbidopa in four divided doses (1:10 or 1:5) Monitor CSF HVA levels

l--HCl Allows lysine absorption Lysinuric 20-30 mg/kg/day in Oral26 Intolerance three divided doses

l- Replenishes serine 3-Phosphoglycerate up to 600 mg/d in sic Oral25 dehydrogenase de- divided doses ficiency

l-Tryptophan Increases kynurenic acid NKH 100 mg/kg/d in three Oral24 which is an endogenous divided doses antagonist of the NMDA receptor

Magnesium Replenishes Mg Primary hypomagne- 0.5-1.5 ml/kg/d MgSO4 IV / oral38 saemia with second- 10% solution IV; oral ary hypocalcaemia maintenance 0.7-3.5 mmol/kg/d elemental Mg in three to five di- vided doses

Mannose Improves CDG Ib (PMI defi- 1 g /kg/d in five di- Oral Not of benefit 42 ciency) vided doses in CDG Ia

Mercap- Chelating agent 15-20 mg/kg/d, up to Oral 26 topropio- max of 1,000 mg/d in nylglycine three divided doses (tiopronin)

Metranida- Reduces propionate pro- Propionic and meth- 7.5-20 mg/kg once Oral19 zole duction by gut ylmalonic acidaemia daily

Miglustat Inhibitor of glucosylcer- Gaucher disease; 100 mg TDSOralOnly recom- 39, 40 (Zavesca) amide synthase, the first neurological mani- mended for enzyme responsible for festations of NPC patients with glycosphingolipid (GSL) mild to mod- synthesis erate Gaucher disease who are unsuitable for enzyme replacement therapy. 630 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

N-Carbam- Stimulates N-acetylgluta- N-Acetylglutamate 100-300 mg/kg/day in Oral 19, 20 oylgluta- mate synthase synthase deficiency, four divided doses mate Carbamoylphos- phate synthase defi- ciency Hyperammonaemia associated with or- ganic acidaemias

Nicotin- Replenishes deficiency 50-300 mg/day Oral26 amide state

Nicotinic Inhibits the release of free Hyperlipidaemia (see Adult dose: 100– Oral32 acid () fatty acids from adipose Chapter 32 for indica- 200 mg 3 times daily, tissue; increases HDL- tions) gradually increased cholesterol over 2–4 weeks to 1–2 g three times daily

NTBC (2-[2- Inhibits 4-hydroxyphe- Tyrosinaemia type I1 mg/kg in one to two OralCombine with 18 nitro-4-triflu- nylpyruvate dioxygenase divided doses low-TYR, low- oro-methyl- PHE diet to benzoyl]-1,3- maintain plas- cyclhexane- ma TYR<600 dione) μmol/l

Octreotide Somatostatin anaologue Persistent hyperinsu- 10 μg/d to 60 μg/d, SC 10 linism given in three or four divided doses or by continuous pump

Pen- Chelating agent Wilson disease; cysti- Wilson disease: up Oral 26, 38 icillamine nuria to 20 mg/kg/day in divided doses (min 500 mg/d); Cystinuria: 2 g/1.73 m2

Pyridoxine Co-factor Pyridoxine-respon- 50-500 mg/d OralPeripheral 21, 22, 29, sive γ-cystathionase Pyridoxine depen- neuropathy 37, 41 deficiency; dency with : can occur with Pyridoxine-respon- 100 mg IV with EEG doses >1000 sive cystathionine monitoring or 30 mg/ mg daily β-synthase (CBS) kg/d for 7 days (main- deficiency; tenance 5-10 mg/d) Pyridoxine depen- dency with seizures; pyridoxine-respon- sive OAT deficiency; X-linked sideroblas- tic anaemia; pri- mary type 1

Pyridoxal- Active co-factor Pyridox(am)ine 5’- 40mg/kg/d in 4 divided Oral29 phosphate oxidase doses deficiency

Riboflavin Coenzyme Glutaric aciduria I, 100 mg/d in two to Oral 12, 13, 15, mild variants of ETF/ three divided doses 23 ETF-DH and SCAD; congenital (complex 1 deficiency) 631 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Selegiline (l- Monoamine-oxidase-B As adjunct to therapy 0.1-0.25 mg/d in three Oral17 deprenyl) inhibitor with 5HT & L-dopa in to four divided doses

BH4 defects

Statins HMG-CoA reductase in- Hyperlipidaemias  Chapter 32 for dis- Oral 32, 33 hibitors has been cussion regarding use used in SLO of individual

Sodium ben- Combines with glycine to Hyperammonaemia 250 mg/d in divided Oral or IV loading 19, 20 zoate form hippuric acid, which doses or by continuous IV dose: 250 mg/ has high renal clearance. IV infusion. kg over 90 min

Removes N2 and reduces Dose may be doubled if severe hyperam- monaemia

Sodium phe- Converted to phenylace- Hyperammonaemia 250-650 mg/kg/d; Oral or 20 nylbutyrate tate, which combines with maximum oral dose IV to form phenyl- 20 g/d glutamine which has high renal clearance

Tetrahyd- Replacement of BH4 Disorders of BH4 syn- 1-3 mg/kg/d in BH4 Oral May be con- 17 robiopterin thesis or recycling; defects; 7-20 mg/kg/d traindicated

(BH4) BH4 responsive forms in PAH def in DHPR defi- of PAH deficiency ciency

Thiamine Co-factor Thiamine responsive 10-15 mg/d Oral Doses of up to 12,19 variants of MSUD, 300 mg have PDH deficiency & been used in complex 1 def CLA; 500-2000 mg/d in thia- mine respon- sive PDH

Triethylene Chelating agent Wilson disease 600 mg/d in divided Oral May reduce 38 tetramine doses increasing to a serum iron (trientine) maximum of 2.4 g/d if – iron supple- necessary ments may be necessary

Triheptanoin Anaplerotic VLCAD deficiency; PC To provide 30% of total Oral 12, 13 deficiency calories

Ubiquinone inborn errors of 100-300 mg/d OralHas been 12

(coenzyme CoQ10 synthesis used in other Q10) mitochondrial cytopathies, but unproven benefit

Uridine Replenishes UMPUMP Synthase de- 100-150 mg/kg/d in Oral36 ficiency (hereditary divided doses orotic aciduria)

Vigabatrin Irreversible inhibitor of Succinic semialde- 50-100 mg/kg/d in two OralUnproven 29 GABA transaminase hyde dehydrogenase divided doses) benefit. Moni- Deficiency tor carefully: increases CSF GABA levels and irrevers- ible visual field deficits pos- sible 632 Appendix A · Medications Used in the Treatment of Inborn Errors

Medication Mode of action Disorders Recommended dose Route Remarks Chapters

Vitamin AFree radical scavenger syn- 100 mg/kg/d Oral30 thetase deficiency

Vitamin CCo-factor; 200-1000 mg/d Oral 18, 30 tyrosinaemia III (4 hydroxyphenylpyru- vate dioxygenase deficiency) Transient tyrosinae- mia of the newborn Glutathione synthase deficiency

Vitamin E Replenishes Glutathione synthase 10 mg/kg/d Oral 30, 32 (alpha to- stores; free radical scav- deficiency copherol) enger Abetalipoprotein- 100 mg/kg/d aemia

Zinc sulfate Increases Zn; impairs Cu Acrodermatitis AE: 30-100 mg Zn/d; Oral38 absorption enteropathica (AE); Wilson disease: 600 Wilson disease mg/d (initial adult dose), 300 mg/d (main- tenance adult dose). Give in three to four divided doses Subject Index

J.-M. Saudubray et. al (Eds.), Inborn Metabolic Diseases, DOI 10.1007/978-3-642-15720-2, © Springer- Verlag Berlin Heidelberg 2012 634 Subject Index

Adenosine 312, 500 Alglucosidase alpha A deaminase 500 – in Pompe 132 – Deficiency 504 Alkaline 417 Abdominal pain 73 Adenosine deaminase superactivity 273 – diagnostic approach 20 506 Alkyl-dihydroxyacetonephosphate Abetalipoproteinaemia 451 503 synthase 600 Abnormal head circumference Adenosine kinase 500 Allan-Herndon-Dudley syndrome 44, – diagnostic approach 36 500, 503 49 Abnormal urine 9, 12 503 Alloisoleucine 90, 282 Acanthocytosis Adenosylcobalamin 386 – in GSD I 120 – diagnostic approach 47 Adenosylcobalamin and Methyl- Allopurinol Acantholysis 547 cobalamin – in treatment in adenylosuccinase 597, 601 – combined deficiencies 390 defect 503 Aceruloplasminaemia 543 Adenosylcobalamin deficiency 392 – in treatment of hypoxanthine-gua- Acetoacetate 218 Adenylate cyclase 126 nine phosphoribosyltransferase Acetoacetyl-CoA 218 503 deficiency 508 – cytosolic 221 Adenylate kinase 2 deficiency 504 – loading test in OTC 98 – mitochondrial 219 Adenylosuccinase 500 Alopecia Acetone 218 Adenylosuccinase deficiency 502 – diagnostic approach 42 Acetonuria Adenylosuccinate 500, 502 Alpers disease 227 – neonatal 12 Adenylosuccinate synthetase 500 Alpha beta 12 487 Acetyl-CoA carboxylase (cytosolic) Adipic 91 Alsin 31 278 Adrenal failure Alternating hemiplegia 178 Acetyl CoA-glucosamine N-acetyl trans- – diagnostic approach 44 AMACR deficiency 56 ferase 582 Adrenaline N-Acyl defi- Acid deficiency 130, 568 – metabolism 411 ciency 481 -deficient Amino acids Niemann-Pick Disease 559 – neonatal 56 597 – transport defects 363 Aconitase 188 – X-linked 56 597 – variations 89, 90 Acrocyanosis Adrenomyeloneuropathy 596 Aminoacidurias 337 – orthostatic 17 Adult polyglucosan body disease – asymptomatic 369 Acrodermatitis enteropathica 548 134 Aminoacylase 2 Acute intermittent porphyria 524 Afamelanotide – deficiency 345 Acute porphyrias 522 – in treatment of erythropoietic proto- Aminoacyl-tRNA synthetases defects Acylcarnitines porphyria 530 231 – in oxidation disorders Agalsidase alpha 567 Aminoadipate aminotransferase 334, 209 Agalsidase beta 567 337 Acyl cholesterol 440 AGAT deficiency (adult versus children) Aminoadipic 337 Acyl-CoA dehydrogenase 9 (ACAD9) 56 Aminoadipic-6-semialdehyde synthase Deficiency 206 AICAR 502 334 Acyl-CoA oxidase deficiency 597 Aicardi-Goutières syndrome 17 Aminoimidazole carboxamide ribotide Acyl-CoA oxidases 600 AICA-Ribosiduria 503 394, 500 Acyl-CoA synthetase deficiency 293 AICAR transformylase 500 Aminolevulinic acid 266, 521 Acyl-CoA transferase 486 89 Aminolevulinic acid dehydratase 522 Acyl-dihydroxyacetone phosphate Alanine glyoxylate aminotransferase – Porphyria 523 600 597, 600 Aminolevulinic acid synthase (ALAS) Acylglycines 91 ALAS2 520 – in fatty acid oxidation disorders 209 – deficiency 521 Aminolevulinic acid synthase, erythroid Adenine 500 Aldehyde oxidase 506 form 522 Adenine phosphoribosyltransferase Aldolase A 129, 160 Amish infantile epilepsy 610 500 158, 160 Ammonia – Deficiency 509 Aldose reductase 142, 414 – Inter-organ Fluxes 301 635 Subject Index A–B

AMP-activated (AMPK) – deficiency 302 ATP synthase 224 129 Arginine 89, 301 Atrioventricular block 20 – deficiency 133 Arginine hydrochloride 305 Attacks of vomiting with lethargy AMP deaminase 500 Argininosuccinate 301 – diagnostic approach 15 – deficiency 503 Argininosuccinate lyase 298 Auriculoventricular block Amylo-1,6-glucosidase 122 – deficiency 302 – neonatal 10 Amylopectin 124 Argininosuccinate synthetase 298 Auto-aggression 41 Anaemia 45 – deficiency 302 Autonomic features 22 – sideroblastic 47 Argininosuccinic acid 89 Autosomal recessive hyper- Anaemias: haemolytic Argininosuccinic aciduria 302 cholesterolaemia 450 – diagnostic approach 47 Aromatic L-aminoacid decarboxylase Anaemias: macrocytic 411 – diagnostic approach 47 Aromatic L-aminoacid decarboxylase B Anaemias: nonmacrocytic deficiency 412 – diagnostic approach 47 21 Anandamide 491 – diagnostic approach 21 Beta-alanine synthase (β-alanine Anaplerosis 189 – neonatal 10 synthase) 514 Andersen disease 123 Arterial tortuosity syndrome 181 291, 488 Anderson disease 452 Arthralgia 22 Basal ganglia/ deposits Angiokeratoma 59 Arthritis – diagnostic approach 38 – diagnostic approach 43 – diagnostic approach 52 Basal ganglia/brain stem hyper- Angioneurotic oedema 22 A 556 intensities Anion gap 12 – deficiency 565 – diagnostic approach 37 Anorexia pseudodeficiency Basal ganglia lesions 63 – diagnostic approach 44 565 Basolateral dibasic amino acid trans- Anserine 424 Ascites porter 364 Antenatal symptoms – diagnostic approach 21 Batten disease 571 – classification 5 – neonatal 10 BCS1L 230 – diagnostic approach 5 Aseptic meningitides 73 Behavioural changes Antiluminal dibasic amino acid trans- Aspartame 254 – in adults 69 porter 364 Aspartate 189, 298, 301 Behavioural disturbances Antiquitin 334, 418 Aspartate aminotransferase 266 – diagnostic approach 35 Antley-Bixler syndrome 469 Aspartate-glutamate carrier 298 Benzoate 305 Apical amino acid transporter system Aspartate-glutamate carrier isoform 1 Benzoquinone acetic acid 273 364 deficiency 39 Betaine 312 ApoA-I 444 Aspartate-glutamate carrier isoform 2 – treatment in cobalamin-C deficiency ApoB-48 440 deficiency 302 391 ApoB-100 440 Aspartoacylase 345 – treatment in 317 ApoC-II 440 583 – treatment in MTHFR deficiency 397 ApoC-III 440 Aspartylglucosaminuria 583 Betaine-homocysteinemethyltrans- Apo D 441 branching enzyme defi- ferase 312 ApoE 440 ciency 134 Beutler test 144 A-I Mutations 452 -III – acute 70 – in fatty acid oxidation defects 212 – isoelectrofocusing 615 – diagnostic approach 17 BH4 441 – episodic 70 – in biopterin metabolism disorders -inducing factor 230 Atkins diet 179 262 Apo-transferrin 541 456 – in DHPR deficiency 262 Arabitol 155 ATP6V0A2 615 – in maternal PKU 260 Arachidonic acid 213, 487 ATP12 Mutation 230 – treatment in PKU 255 Arachidonoyl 487 ATP-binding cassette (ABC) protein BH4 loading test 261 Arginase 298 A1 444 BH4-Responsive PKU/HPA 254 636 Subject Index

Bicycle ergometer test 99 Brain glycogenosis 133 Cardiac arrest 21 Bile acid amidation defect 1 481 Brain metabolism 406 – neonatal 10 Bile acid amidation defect 2 481 Brain stem nuclei lesions 63 Cardiac dysrhythmia Bile acid CoA 481 Beta-ureidoisobutyrate – diagnostic approach 20., 41 Bile acid-CoA: amino acid N-acyl trans- (β-ureidoisobutyrate) 514 Cardiac failure ferase 474 Beta-ureidopropionate – diagnostic approach 20, 41 Bile acid CoA Deficiency 481 (β-ureidoisobutyrate) 514 – emergency management 109 Bile acid replacement therapy 477 Branched-chain 2-ketoacid dehydro- – neonatal 10 Bile acid sequestrants 440, 457 genase complex 278, 281 Cardiac glycogenoses 127 Bile acid synthesis Branched-chain amino acids 89 Cardiac presentation – disorders 473 – catabolism 278 – neonatal diagnostic approach 10 – pathway 474 Branched-chain organic acidurias 277 Cardiac tamponade Bile acid transporter Branching enzyme (astrocytes) 129 – neonatal 10 – ileal 440 Branching enzyme deficiency 123 487 Bile alcohols 478 Bratton-Marshall test 503 Cardiolipin remodelling enzyme Biocytin 378 Brittle hair Deficiency 488 Biopterin metabolism 262 – diagnostic approach 42 Cardiolipin synthase 486 – disorders with hyper- Brody disease 547 phenylalaninaemia 260 Brown-Vialetto-van Laere syndrome – diagnostic approach 21, 41 Biotin cycle 376 10, 207 – neonatal 10 Biotin deficiency Bundle branch blocks Carnitine – acquired 380 – neonatal 10 – in emergency management 107 Biotin-dependent 376 Burst-suppression EEG pattern 9, 354, – in 3-methylcrotonyl glycinuria 290 Biotinidase 376 351 – in Isovaleric aciduria 287 Biotinidase deficiency 56, 377 Butyrylcarnitine 292 – treatment in fatty acid oxidation – classification 381 defects 212 – screening 84 – treatment in lysinuric protein intoler- Biotin-responsive basal ganglia disease C ance 368 378 Carnitine acylcarnitine Biotin-responsive disorders 375 202 Biotin-sensitive transporter hTHTR2 C7orf10 gene 342 – deficiency 204 379 CAFSA syndrome 583 Carnitine concentrations Biotinyl-5’-AMP 376 Calcinosis – in fatty acid oxidation defects 209 Bisphosphoglycerate 163 – familial tumoral 610 Carnitine cycle defects 203 Bjornstad syndrome 226 Calcium-channel blockers Carnitine palmitoyltranferase 202 Crisis – in hyperinsulinism 171 Carnitine palmitoyltransferase I (CPT I) – diagnostic approach 22 Calcium folinate 262 – deficiency 204 Bone marrow transplantation Calcium/Manganese transporters Carnitine palmitoyltransferase II (CPT II) – in adenosine deaminase deficiency – disorders 547 – deficiency 204 505 Calmodulin 126 Carnitine transporter 202 – in Farber disease 568 CAMP-dependent protein kinase 126 – deficiency 203 – in Krabbe disease 565 Canavan disease 345 Carnosinase 424 – in Metachromatic leucodystrophy Carbaglu 306 – deficiency 408 566 Carbamoylphosphate synthetase 511 Carnosine 424 – in mevalonic aciduria 464 Carbamoylphosphate synthetase 1 298 Cataplectic attacks Bone necrosis – deficiency 302 – in Niemann-Pick type C 570 – diagnostic approach 52 Carbamyl glutamate 306 Cataract 72, 73 Beta-oxidation defects (β-oxidation) – in Methylmalonic aciduria 287 – diagnostic approach 49 202, 205 – in Propionic aciduria 287 Catatonia Boxing movements 9 Carbidopa 262 – in adults 69 Brain dysplasia and malformations Carbonic anhydrase XII deficiency 18 Catecholamine 252 – diagnostic approach 38 Carbonyl reductase 414 – in Menkes disease 540 637 Subject Index B–C

Catecholamine 412 Cherry red spot 72, 73 188 Catechol-O-methyltransferase 411 – diagnostic approach 40 298 Cathepsin D Chilblains 17 – deficiency 302 – deficiency 573 CHILD syndrome 466 Citrullinaemia type 1 302 Cathepsin K 588 Chitotriosidase Citrullinaemia type 2 302 CDG – in Gaucher disease 558 Citrulline 89 301, 358 – nomenclature 609 – in Niemann-Pick type A/B 560 – treatment in lysinuric protein – see congenital disorders of glyco- – in Niemann-Pick type C 570 intolerance 368 sylation 609 Chloropropionate CIV assembly deficiency 230 CDG Classification 609-611 – in respiratory chain 235 CK syndrome 469 CDG-Ie 611 Chloroquine Claudin CDG-Im 611 – treatment in porphyria cutanea tarda – deficiency in hypomagnesaemia with CDG-plus 615, 616 527 hypercalciuria and nephrocalci- CDP diacylglycerol 487 Cholestanepentol glucuronides 479 nosis 546 CEDNIK syndrome 5 Cholestanol 478 CMP-sialic acid transporter 611 Cephalalgia Cholestatic jaundice – deficiency 611 – in adults 61 – diagnostic approach 48 CM remnant 440 Cephalhaematoma 37 – neonatal 10 Coagulopathy – diagnostic approach 36 Cholesterol 474 – neonatal 10 Ceramide 492, 556 Cholesterol 7α-hydroxylase 474 Coarse facies Ceramide 492 – deficiency 450, 482 – diagnostic approach 6 Ceramide trihexoside 567 Cholesterol absorption inhibitors 440 – neonatal 10 Cerebellar ataxia 34, 70 Cholesterol ester transport protein Cobalamin metabolism 386 – chronic 70 (CETP) 442 – absorption disorders 387 – diagnostic approach 35 Cholesterol storage – transport disorders 387 – in adults 69 – in Niemann-Pick type C 570 Cobalamin A 392 Cerebellar haemorrhage 15 Cholesterol synthesis Cobalamin adenosyltransferase Cerebellar syndrome 32 – pathway 462 283,392 Cerebral Folate Deficiency 395 – disorders 461 Cobalamin-B 392 Cerebral transporter (GLUT1) Cholesterol transport Cobalamin-C 56 390 deficiency 56 – pathway 444 Cobalamin-D 391 Cerebral organic acid disorders 333 Cholesteryl esters 440 Cobalamin-E 393 Cerebroside 556 Cholesteryl ester storage disease 447 Cobalamin-F 390 Cerebroside β-galactosidase Cholesteryl ester transfer protein defi- Cobalamin-G 393 – deficiency 564 ciency 453 Cobalamin transport 386 Cerebrotendinous xanthomatosis Cholestyramine 457 – disorders 385 (CTX) 478 Cholic acid Coenzyme Q10 224 Cerebrovascular accident 15 – in bile acid synthesis defects 476 – in respiratory chain 235 Ceroid lipopigments 572 Choline – deficiency 56 Ceruloplasmin – catabolism 432 COG7 deficiency 615 – in aceruloplasminaemia 544 deficiency 491 Colesevalam 457 – in Menkes disease 540 Chondrodysplasia punctata 2 465 Colestid 457 – in Wilson disease 538 Chondrosarcomas 614 Colestipol 457 CH3succinic 91 Chorea 62 Collybistin 409 Channelopathies Choreoathetosis 34 Coma – in hyperinsulinism 169 retention disease 452 – diagnostic approach 7, 15, 16 Charcot-Marie-Tooth disease 440 – in adults 60 – in adults 64 – physical-chemical properties 441 – neonatal 7 Chemokine CI assembly proteins deficiency 230 Combined defect of mitochondrial and – in Gaucher disease 558 CIII assembly proteins deficiency 230 peroxisomal fission 597 Chenodeoxycholic acid Combined deficiency of XO, AO and – in bile acid synthesis defects 476 – diagnostic approach 48 sulfite oxidase 506 638 Subject Index

Combined degeneration of the spinal Corneal arcus 454 Cystine porter 618 cord 32 Corneal clouding 72, 73 Cystinosin 618 Combined Hyperlipidaemia and the – diagnostic approach 51 Cystinosis 617 small dense LDL syndromes Corneal opacities – infantile 618 – familial 447 – diagnostic approach 51 – intermediate 622 Complex I 224 Corpus callosum agenesis 38 – ocular 622 Complex II 224 Cortical cysts 6 Cystinuria 363, 364 Complex III 224 Cortical heterotopia 6 Cytidine 511 Complex IV 224 Corticospinal tract involvement 32 Cytidine deaminase 511 Complex V 224 Costeff optic atrophy syndrome 291 – deficiency 514 Complex molecules Cramps 19 Cytidine kinase 511 – Disorders 5 Creatine 240 Cytidine monophosphate 511 Conduction defects Creatine deficiency syndromes 239 Cytidylmonophosphate 486 – diagnostic approach 21 240 Cytidyltriphosphate 486 – neonatal 10 Creatine phosphate 240 Cytochrome c 224 Confusion Creatine substitution Cytochrome-c oxidase 224 – in adults 61 – in cerebral creatine defects 244 Cytosolic 5‘- Superactivity Congenital adrenal hyperplasia Creatine synthesis and transport 240 514 – screening 85 Crestor 456 Congenital disorders of glycosylation Crotonase 334 607 Crotonyl-CoA 334 D Congenital disorders of protein CTX 56 N-Glycosylation 612 Cubam 387 Congenital disorders of protein Cubilin 387 D-2-hydroxyglutarate 344 O-Glycosylation 614 Cutaneous porphyrias 522 D-2-hydroxyglutarate succinic semi- Congenital dyserythropoietic anaemia Cutis laxa 615 aldehyde 408 type II 611 Cutis laxa type 2 611 D-2-hydroxyglutaric aciduria 343 Congenital disease 6 CV assembly proteins deficiency D- and L-2-hydroxyglutaric aciduria Congenital hypothyroidism 230 – combined 344 – screening 85 Cyclical vomiting 17 132 Congenital muscular dystrophy 610 Cyclic pyranoptrin monophosphate Darier-White disease 547 Connexins defects 39 507 D-bifunctional protein 600 Conradi-Hünermann syndrome 465 Cystagon 622 – deficiency 597 Conserved oligomeric golgi (COG) Cystathionine β-synthase 312 Deafness 72 complex 615 – deficiency 56 ,313 – diagnostic approach 36 – defects 611 – screening 83 Debranching enzyme 129 Cystathionine 312 – deficiency 122, 133 – diagnostic approach 45 319 Dehydration Copper metabolism 536 Cysteamine 618, 622 – diagnostic approach 18, 19 – transport disorders 535 Cysteamine bitartrate 622 – emergency management 105 Copper histidine 312, 618 Dehydrocholesterol 462 – in Menkes disease 540 Cysteine-cysteamine Dehydrocholesterol reductase Copper-requiring enzymes 539 – disulfide 618 deficiency 464 Copper storage disorders 540 Cysteine proteinase 588 Dehydrodolichyl diphosphate Coproporphyrin 521 Cysteinylglycine 424 synthetase deficiency 37 Coproporphyria 528 Cysteinyl leukotriene 426 Dehydrogenase 500 Coproporphyrinogen oxidase 522 Cystic fibrosis Deiodinases 547 – deficiency 528 – screening 85 Delirium 18 CoQ-cytochrome-c reductase 224 Cystic leukoencephalopathy 37 34 Cord blood transplantation Cystine 89 Dentate nuclei lesions 63 – in Krabbe disease 565 Cystine/dibasic amino acid transporter Dentate nuclei of the cerebellum Cori disease 122 364 hyperintensities 38 639 Subject Index C–E

Deoxyadenosine 504 – E3 191 D-Penicillamine deficiency – E3 deficiency 194, 282 – in cystinuria treatment 366 230, 509 Dihydrolipoamide transacetylase 192 Duarte variant () 144 Deoxymethylsphingosine 492 Dihydrolipoyl acyltransferase 282 Duranin gene 343 Deoxysphingoid bases 493 Dihydroneopterin triphosphate 411 D-xylulose 153 Deoxysphingosine 492 Dihydroorotate dehydrogenase Dynamin like protein 1 231, 593 Deoxythymidine monophosphate 394 – deficiency 512 – deficiency 231 Deoxyuridine monophosphate 394 Dihydropteridine reductase 252 Dynamin-related GTPase 230, 231 Deoxyuridine suppression test 387 – deficiency 260 Dysautonomia 73 Dephosphorylation/ Dihydropyrimidinase 511 – in adults 67 system – deficiency 513 Dysbetalipoproteinaemia 450 – PDHE1 191 Dihydropyrimidine dehydrogenase Dyskeratosis 547 Dermatan sulfate 583 511 Dyslipidaemia 439 Desmosterol 462 – deficiency 513 – treatment 454 Desmosterolosis 467 Dihydrosphingosine 492 Dysmorphism Desmosterol reductase deficiency 467 Dihydrothymine 513 – diagnostic approach 7 Developmental delay Dihydrouracil 513 Dysostosis multiplex 584 – diagnostic approach 27 Dihydroxyacetone phosphate 160 neonatal 10 Dextrometorphan Dihydroxyacetone phosphate acyltrans- Dysplasia 6 – in treatment of NKH 354 ferase 592,600 – diagnostic approach 7 (and pseudo diabetes) Dihydroxyadenine 509 34, 62 – diagnostic approach 44 Dihydroxycholestanoic acid 598, 599 – in adults 61 Diacylglycerol 487 Dihydroxycoprostanic acid 480 Dystonic tremor 178 Diacylglycerolacetyltransferase 486 Dihydroxyhexanoic acid 408 Diacylglycerol 486, 487 Dimethylglycine 434 Diaminobenzidine procedure 602 Dimethylglycine dehydrogenase E (chronic) – deficiency 431, 434 – diagnostic approach 45 Dimethyl sulfide 317 Diazoxide Dinitrophenylhydrasine 12 E1 kinase 191 – in hyperinsulinism 171 Dipeptidase 213 E1 phosphatase 191 Dibasic amino acids 364 – deficiency 428 E3BP 192 Dicarboxylic acids 91 Dislocation of the lens Encephalopathy – in fatty acid oxidation disorders 209 – diagnostic approach 51 – early myoclonic: diagnostic Dicarboxylic 369 Distal with rimmed vacuoles approach 9 Dicarboxyl porphyrin 521 615 – in adults 60,61 Dichloroacetate Disulfide cysteine-homocysteine 90 Easy bruising – in emergency management 109 Divalent-metal transporter DMT1 541 – diagnostic approach 43 – in PDH deficiency 194 – deficiency 544 Ectopia lentis – in respiratory chain 235 Docosahexaenoic acid 603 – diagnostic approach 51 Dienoyl-CoA reductase 202 Dodecenoyl-CoA delta 202 Ectopic calcification 468 – deficiency 206 Dolichol phosphate 608 Ehlers-Danlos syndrome Dihydrobiopterin 252 Dolichol synthesis – progeroid variant 610 Dihydroceramide 492 – defect 611 Electron transfer defects 206 Dihydroceramide desaturase 492 Dolichostenomelia 313 Electron transfer flavoprotein 202, 432 Dihydroceramide synthase 492 Dopa-decarboxylase inhibitor 262 Dihydrofolate 394 – in dopa-responsive dystonia 415 – in Gaucher type I 559 394 Dopamine 252 Emergency Treatments 103 – deficiency 397 – metabolism 411 Emopamil 466 Dihydrolipoamide acyltransferase defect 415 Endocannabinoid 2-arachidonoyl – E2 191 Dopamine β-hydroxylase 411 glycerol 490 Dihydrolipoamide dehydrogenase – deficiency 413 282 Dopa-responsive dystonia 59, 414 – deficiency 454 640 Subject Index

Energy metabolism Eye movements Focal islet cell hyperplasia 169 – disorders 4 – diagnostic approach 40 Folate carrier Enoyl-CoA hydratase 205, 334 Eye of the tiger sign 543 – reduced 394 Entacapone 262 457 Folate/Folic acid metabolism 394 – in BH4 defects 262 Folate receptors 394 Enteral feeding Folate transport – in emergency management 106 F – disorders 385 Enzyme replacement therapy Folate transporter 394 – in Gaucher disease 558 – protein-coupled 394 – in Pompe 132 Fabry disease 57, 566 Folic acid 394 – in Fabry disease 567 – screening 85 – treatment in folate transport defects – in Niemann-Pick type B 560 Facilitative glucose transporters 176 395 – in adenosine deaminase deficiency Failure to thrive Folinic acid 262 505 – diagnostic approach 44 – in DHPR deficiency 262 Epilepsy 67 Fanconi-Bickel Syndrome 180 – treatment in folate transport defects – diagnostic approach 27, 33 – diagnostic approach 50 395 Epilepsy, progressive myoclonus 2a Farber disease 568 Folinic acid-responsive epilepsy 9 (EPM2A) 134 Farnesyl-PP synthase 462 Forbes disease 122 Epilepsy, progressive myoclonus 2b Fasting ketoacidosis 23 Forearm exercise test 99 (EPM2B) 134 Fasting test 96 Formiminoglutamate 394 Epoxyoctanedioic 91 – in fatty acid oxidation defects Formiminotetrahydrofolate cyclode- Erythritol 155 210 aminase 394 Erythrodontia 526 Fatigue 19 Formylaminoimidazolecarboxamide Erythropoietic porphyria 522 ,525 Fatty acid 2-hydroxylase 492 ribotide 394, 500 Erythropoietic protoporphyria 529 – deficiency 490 494 Formylglycinamide ribotide 394 Essential fructosuria 159 Fatty acid β-oxidation oxidation Free cholesterol 440 Essential pentosuria 153 dis orders 201 Friedreich ataxia ETF ubiquinone – screening 84 – in adults 69 202,432 – peroxisomal 599 158 Ether- biosynthesis 600 Fatty acid transport defects 203 -1,6-bisphosphatase deficiency Ether- 592 Fatty acid α-oxidation 599 162 Ethyleneglycol 91 Fatty aldehyde dehydrogenase Fructose-1,6-bisphosphate aldolase Ethylhydracrylic 92 213 160 Ethylmalonic 91 Fazio-Londe disease 207 Fructose-1-phosphate 160 Ethylmalonic semialdehyde dehydro- FBXO7 Fructose intolerance (hereditary) 160 genase – mutations 415 Fructose metabolism 158 – deficiency 292 Ferritin 541 – disorders 157 Exchange Transfusion Ferrochelatase 522 Fructosuria 159 – in emergency management 108 – deficiency 529 Fucosidase 583 Exercise-induced hyperinsulinism 170 541 Fucosidosis 583, 587 Exercise intolerance – deficiency 543 Fumarase 188 – diagnostic approach 18 Fibrates 458 195 Exercise test 99 Fibric acid derivatives 440,458 Fumarylacetoacetase 266 Exopeptidase prolidase 429 Filipin staining test 570 Exostoses 614 Fish eye disease 453 Exostosin-1/exostosin-2 614 Fish odour syndrome 433 G Exostosis (hereditary multiple) Flavin adenine dinucleotide 188, – diagnostic approach 51 202 Extracorporeal toxin-removal Proce- Flavin-containing monooxygenase 3 GABA /GABA conjugates 406, 407 dures 432 GABA Receptor Mutations 410 – in emergency management 107 Flippase 609 GABA transaminase 406 Extrapyramidal signs 32, 34 456 – inhibitor 408 641 Subject Index E–G

Galabiosylceramide 556 Glucagon – deficiency 339 Galactitol 142 – in hyperinsulinism 171 Glutaryl-CoA oxidase deficiency 601 Galactocerebrosidase 556 Glucocerebrosidase 558 Glutathione 423 – deficiency 564 556 – disorders in the metabolism 425 Galactocerebroside 556 – metabolism 424 142 – overactivity 169 424 – deficiency 148 Glucokinase (GK) mutations – deficiency 425 Galactolipids 143 – in hyperinsulinism 170 Glyceraldehyde 160 Galactonate 142 189 Glyceraldehyde-3-phosphate 163 Galactoproteins 143 Glucose-6-phosphatase 129,117 Glyceraldehyde-3-phosphate dehydro- Galactosaemia Glucose-6-phosphate dehydrogenase genase 163 – classic 143 deficiency 152 Glyceric acid 91 – screening 83 – screening 85 Glycinamide ribotide 394 Glucose-6-phosphate translocase 129 Glycine 89, 358, 409 – 142 Glucose/Galactose 177 – in emergency management 107 – disorders 141 Glucose loading test 98 – in 3-methylcrotonyl glycinuria 290 Galactose-1-phosphate 142 Glucose sensor 168 350 Galactose-1-phosphate uridyltrans- Glucose transport 176 Glycine cleavage system hydrogen ferase 142 – disorders 175 carrier protein Galactose-1-phosphate uridyltrans- deficiency – H-protein 352 ferase deficiency 143 syndrome 178 Glycine-conjugated bile acids 477, Galactose dehydrogenase 142 Glucosidase I 609 482 Galactosialidosis 583, 587 558 349 Glucosylceramide 556 Glycine metabolism 350 – deficiency 564 Glucosyltransferase I 609 Glycine N-methyltransferase 312 Galactosylceramide 556 – deficiency 613 Glycine N-methyltransferase deficiency Galactosylceramide synthase Glucosyltransferase II 609 318 492 Glucuronic acid pathway 153 Glycine receptor 409 Galactosylsphingosine 564 Glucuronides 478 Glycinergic synapse 409 Gallstones GLUT1 deficiency 178 Glycine transamidinase 326 – in erythropoietic protoporphyria GLUT2 deficiency 129 180 409 529 GLUT10 deficiency 181 Glycine uptake 409 Gamma amino butyric acid trans- Glutaconyl-CoA 339 Glycinuria 369 aminase deficiency 407 Glutamate 189 depletion syndromes 132 GAMT deficiency 57 – synthesis 324 129 Gangliosides 492, 556 168, 298, Glycogenin-1 132 Gaucher disease 557 301 – deficiency 132 Gaze palsies 72, 73 – overactivity 169 Glycogenin-2 132 458 Glutamate formiminotransferase 394 Glycogen metabolism 116 – deficiency 396 Glycogenosis type IV 57 – in adenosine deaminase deficiency decarboxylase 406 Glycogen 122 505 298, 301 – deficiency 125 – in X-linked ALD 603 Glutamine 89, 301 Glycogen storage diseases 115 Gephyrin 409 298 – classification 129 Geranyl-PP synthase 462 Glutaric acid 91 – Type 0 126 73 57,337,334 – Type I 117 Globoid cell leukodystrophy 563 339 – Type II 130 Globoside 556 Glutaric aciduria type II 206 – Type III 122, 133 Globotriaosylceramide 556 Glutaric aciduria Type III 342,597 – Type IV 123 Globotriasylceramide 567 Glutarylcarnitine 339 – Type V 127 Glossitis Glutaryl-CoA 334 – Type VI 125 – diagnostic approach 52 Glutaryl-CoA dehydrogenase 334 – Type VII 128 642 Subject Index

– Type IX 125 Gunther disease 525 – ferroportin-related (type 4) 543 deficiency 126, Gyrate atrophy of the choroid 325 Heparan N-sulfatase 580, 582 132 Gyration abnormalities 38 Heparan sulfate 583 Glycolic 91 Hepatic coma 17 deficiency 451 – disorders 128 H Hepatic porphyrias 522 608 Hepatic presentation – catabolism 586 – diagnostic approach 10 Glycosaminoglycans 580, 583 HABC syndrome 39 – neonatal 10 Glycosphingolipid 556 Haem A Hepatic transplantation (see trans- Glycosphingolipid biosynthesis 492 – farnesyltransferase 230 plantation) – disorders 485, 493 Haem arginate 525 Hepatitis-like episodes Glycosylphosphatidylinositol 609, 610 Haematin 525 – neonatal 10 557 Haematopoietic cell transplantation Hepatocellular necrosis Glycylproline 429 – in X-linked ALD 603 – neonatal 10 Glyoxylate 601 – in adenylate kinase deficiency 504 Hepatoerythropoietic porphyria 528 Glyoxylate detoxification 599, 600 – in GM1 ganglioside 556 deficiency 514 – neonatal 10 GM1 gangliosidosis 57, 561 Haem biosynthesis – diagnostic approach 48 GM2 activator protein 562 – pathway 520 Hepatorenal tyrosinaemia 267 GM2 ganglioside 556 – disorders 519 Hepatosplenomegaly 6 GM2 Gangliosidosis 57, 562 Haemin therapy 524, 542 – diagnostic approach 48 – deficiency 241 Haemochromatosis 542 – neonatal 10 GM3 ganglioside 492 556 Haemodialysis Hepcidin 541 GM3 synthase 492, 610 – in emergency management 108 Hereditary coproporphyria 528 – deficiency 494, 615 Haemofiltration Hereditary folate malabsorption 395 Golgi-associated secretory pathway – in emergency management 108 Hereditary fructose intolerance 159 (SPCA) 547 Haemoglobinopathy Hereditary haemochromatosis (Type 1) GRACILE syndrome 226 – screening 85 – classic 542 Granulocyte colony-stimulating factor Haemojuvelin 541 Hereditary haemochromatosis (Type 2) – in GSD Ib 120 – deficiency 544 – juvenile 542 Greenberg skeletal dysplasia 468 Haemolytic anaemias 45 Hereditary haemochromatosis (Type 3) Growth hormone deficiency 44 Haemolytic uraemic syndrome 50 – TfR2-related 543 GTP cyclohydrolase 411 Haemophagocytosis 47 Hereditary haemochromatosis (Type 4) – deficiency 260 – diagnostic approach 47 – ferroportin-related 543 Guanidinoacetate 240 Haemoxygenase 541 Hereditary inclusion body myopathy Guanidinoacetate methyltransferase Hailey-Hailey disease 547 611 240 Hallucinations 18 Hereditary multiple exostoses 614 deficiency 241 Hand-foot syndrome 22 Hereditary neuropathy Guanidinobutyrate 408 Haptocorrin 387 – in adults 64 Guanine 500 Haptocorrin (R Binder) deficiency 388 Hereditary orotic aciduria 512 500 Hartnup disorder 363, 368 Hereditary paraganglioma 229 -mannose Hawkinsinuria 274 Hereditary progressive dystonia with 608 HDL marked diurnal fluctuation 414 Guanosine kinase 500 – synthesis 444 Hereditary tyrosinaemia type I 267 500 Heart failure 20 Hereditary tyrosinaemia type II 271 252 HELLP syndrome Hers disease 125 Guanosine triphosphate cyclohydrolase – diagnostic approach 45 Hexanoylglycine 91 252 Haemochromatosis (type 1) Hexosamine 580 – deficiency 414 – classic (type 1) 542 Guillain-Barré syndrome – juvenile (type 2) 542 – deficiency 562 – in adults 64 – TfR2-related (type 3) 543 HHH syndrome 302, 328 643 Subject Index G–H

HHHH syndrome 39, 52 Hydroxy-3-methylglutaryl-CoA lyase – emergency management 105 Hiccups 9 278 – hyperinsulism/hyperammonaemia High-density (HDL) 444 – deficiency 219 (HI/HA) syndrome 170 – HDL-2 physical-chemical properties Hydroxy-3-methylglutaryl coenzyme A Hyperargininaemia 302 441 218 Hyperchlohidrosis 18 – HDL-3 physical-chemical properties Hydroxyacyl-CoA dehydrogenase 334, Hypercholesterolaemia 449 441 600 – familial 448 High signal of basal ganglia 59 Hydroxyadipic acid 337 Hyperekplexia 408 Hippurate 305 Hydroxybutyrate 218, 408 Hyperglycaemia 23 Histidine 424 89 Hydroxy-butyrate/acetoacetate ratio Hyper-IgD and periodic fever syndrome HMG-CoA lyase 218 95 463 HMG-CoA reductase 462 440 Hydroxybutyrate dehydrogenase 218 Hyperimidodipeptiduria 429 HMG-CoA reductase inhibitors 440 Hydroxybutyric acid 91 Hyperinsulinaemic Hypoglycaemia HMG-CoA synthase 218, 462 Hydroxybutyric aciduria 407 167 H-NMR spectroscopy 95 Hydroxychloroquine Hyperinsulinism Holocarboxylase synthetase 376 – treatment in porphyria cutanea tarda – diagnostic approach 44 – deficiency 377 527 Hyperinsulism/hyperammonaemia (HI/ Homocarnosine 408, 424 Hydroxycholesterol 474, 481 HA) syndrome 170 Homocarnosinosis 408, 429 Hydroxycyclohexylacetate 274 Hyperkeratosis-dyskeratosis Homocitrulline 90, 328 Hydroxy-dicarboxylic acids 92, 342 – diagnostic approach 42 Homocitrullinuria 328 Hydroxy-glutaric 92 Hyperketosis 88 – triple H syndrome Hydroxyindolacetic acid 411 Hyperlactataemia 88 Homocysteine 312 Hydroxy-isobutyric 92 – diagnostic approach 24 – hyperhomocysteinaemia differential Hydroxyisobutyric acid dehydrogenase – emergency management 109 diagnosis 315 278 Hyperlipoproteinaemia – plasma total 315 Hydroxyisobutyric aciduria 292 – type III 450 Homocysteine-cysteine mixed disulfide Hydroxyisobutyryl-CoA deacylase 278 Hyperlysinaemia 336 314 – deficiency 293 Hypermanganesaemia Homocystine 89 Hydroxyisovaleric acid /Hydroxy- – isolated autosomal recessive 547 Homocystinuria 313 isovalerate 92,282 ,290 Hypermethioninaemia 317 – screening 83 Hydroxyisovaleryl carnitine 290 Hyperornithinaemia 325, 328 Homogentisate 273 Hydroxylysinaemia 337 Hyperoxaluria 597 Homogentisate dioxygenase 266 Hydroxylysine 334 Hyperoxaluria type 1 597 Homogentisic 91 – catabolic pathways 334 Hyperphenylalaninaemia 251 Homovanillic acid 411 Hydroxylysine kinase 334, 337 – classification 254 Homozygous hypobetalipoprotein- Hydroxylysinuria 337 Hyperprolinaemia type I 359 aemia 452 Hydroxymethylbilane 526 Hyperpyruvicaemia 26 582, 582 Hydroxymethylbilane synthase 524 Hurler/Scheie 582 Hydroxy-N-butyric 91 – diagnostic approach 44 581, 582 Hydroxyphenyl-acetate 271 Hypertonic episodes 9 Hyaluronic acid 583 Hydroxyphenyl-lactate 271 Hypertriglyceridaemia 582 Hydroxyphenyl-pyruvate 266, 271 – familial 446 Hydratase 600 Hydroxyphenylpyruvate dioxygenase Hyperuricaemia Hydroperoxyeicosatetraenoic acid 266 – diagnostic approach 27 213 Hydroxypropionate/propionic 92 ,282 Hyperventilation attacks Hydrops 468 Hydroxytryptophan 411 – diagnostic approach 51 6 – in biopterin metabolism disorders Hyperzincaemia – neonatal 10 262 – autosomal dominant, without Hydroxocobalamin 386 Hyperammonaemia 13 328 symptoms 549 – in cobalamin transport disorders – differential diagnosis 304 – hyperzincaemia with hypercal- 387 – emergency management 107 protectinaemia 549 Hydroxy-3-methyl-glutaric 93 – acquired disorders 304 Hypoacetylaspartia 346 644 Subject Index

Hypoalphalipoproteinaemia IDL 440 Iridodonesis 313 – familial 452 Iduronate sulfatase 580 Iron Hypobetalipoproteinaemia 451 Iduronidase 582 – transport disorders 535 – familial 451 Imerslund-Gräsbeck syndrome 387 Iron deficiency syndromes 544 Hypochloraemic alkalosis Imidazole dipeptide 423 Iron metabolism 541 – diagnostic approach 50 – disorders 428 Iron protoporphyrin 520 Hypocholesterolaemia – metabolism 424 Iron-refractory iron deficiency anaemia – diagnostic approach 45 Imidodipeptides 429 544 Hypodontia 559 Ischaemic forearm exercise test 128 – diagnostic approach 52 369 Ischaemic stroke Hypoglycaemia 23, 88 Immune deficiency – in adults 61 – diagnostic approach 26 – diagnostic approach 49 Islet cell hyperplasia 170 Hypoglycorrhachia 179 IMP cyclohydrolase 500 – diffuse/focal Hypogonadism sterility Inborn errors revealed in the neonatal Isobutyrylcarnitine 292 – diagnostic approach 44 period and early in infancy Isobutyryl-CoA dehydrogenase Hypoketosis 88 – classification 13 278 Hypomagnesaemia Inclusion body myopathy 615 – deficiency 292 – isolated autosomal recessive 546 Indian childhood cirrhosis 540 Isocitrate dehydrogenase 188 – isolated dominant 546 Infantile ascending hereditary spastic – Isocitrate dehydrogenase 1 defi- – with hypercalciuria and nephrocalci- paralysis 31 ciency 344 nosis 545 Infantile free sialic acid storage disease – Isocitrate dehydrogenase 2 defi- – with secondary hypocalcaemia 545 587 ciency 344 Hypomyelination Infantile neuroaxonal dystrophy 489, – Isocitrate dehydrogenase (IDH3) – diagnostic approach 39 543 deficiency 197 Hyponatraemia Infantile 595 Isofagomine – in acute intermittent porphyria 524 Inflammatory bowel disease 46 – in Gaucher type I 559 Hypoparathyroidism Inflammatory syndrome 17 Isoflavones 145 – diagnostic approach 44 – neonatal 10 90, 278 Hypothyroidism Inflammatory syndrome Isopentenyl-PP 462 – diagnostic approach 44 – diagnostic approach 49 Isopentenyl-PP isomerase 462 Inosine monophosphate 500 Isoprenoid synthesis – diagnostic approach 9, 11 Inosine triphosphatase deficiency – pathway 462 – neonatal 9 510 Isovaleric acid 282 Hypotonia cystinuria syndrome 9 ,365 Insulin Isovaleric aciduria/emia 279, 287 Hypouricaemia – in emergency management 106 Isovalerylcarnitine 282 – diagnostic approach 27 Insulin secretion 168 Isovaleryl-CoA 282 Hypoxanthine 500, 507 Intermediate-density lipoproteins (IDL) Isovaleryl-CoA dehydrogenase 282, Hypoxanthine-guanine phosphoribo- – physical-chemical properties 441 278 syltransferase 500 Intestinal obstruction Isovalerylglycine 282 92 – deficiency 507 – diagnostic approach 45 ISSD (infantile sialic acid storage Hysteria 17 Intestinal riboflavin transporter 206 disease) 583 Intoxication – disorders 4 I Intracranial hypertension 15 J Intractable convulsions – emergency management 109 I cell disease 582 ,587 Intrauterine growth retardation 6 Jansky-Bielschowsky disease 571 Ichthyosis, 59 – diagnostic approach 6 Jaundice – diagnostic approach 42 Intrinsic factor deficiency 387 – neonatal 10 Idebenone Inward rectifying potassium channel contractures – in respiratory chain 235 – diagnostic approach 52 Idiopathic copper toxicosis 540 – defects 169 Joubert syndrome 38 645 Subject Index H–L

Lactate/pyruvate ratio 95 Leukopenia K Lactate synthesis 24 – diagnostic approach 47 92 Leukotriene metabolism 213 K+-ATP channel (KIR) 168 Lactic acidosis 24 – defects 214 Kayser-Fleischer rings 537 Lactobionate 145 Levodopa 415 Kearns-Sayre syndrome 227 Lactose 142 -defective ApoB Keratan sulfate 583 Lactosylceramide 556 – familial 449 Keratitis Lactosylceramide synthase 492 Lipase – diagnostic approach 51 Lactosylceramide-α-2,3 – hepatic 440 Keratosis follicularis 42, 547 494 615 glycosylation Ketoacid dehydrogenase complex 191 Lafora disease 133 – defects 615 ,610 Ketoacidosis 13, 23 Laforin-malin complex 129, 133 LIPN1 deficiency 487 – emergency management 105 Lamin B receptor 469 – Lipin 1 mutation in statin treatment Ketoacyl-CoA thiolase 205 LAMP-2 129 456 Ketogenesis – deficiency 132 Lipitor 456 – biochemical pathways 218 Landing disease 561 Lipoamide dehydrogenase – disorders 217 Lanosterol 462 – L-protein 352 Large-amplitude tremors 9 Lipodystrophy 43 – in GLUT1 deficiency 179 L-arginine Lipogenesis 189 Ketoglutarate dehydrogenase complex – in emergency management 107 191 (KDHC) 191 457 – lipoic acid metabolism defect 198 – deficiency 195 Lathosterol 468 (a) Ketohexokinase 159 Lathosterolosis 468 – elevated 454 Ketoisocaproic acid 282 L-carnitine (see carnitine) (LPL) 442, 440 Ketolysis 218 L-citrulline (see citrulline) – deficiency 445 – biochemical pathways 218 L-dihydroxyphenylserine Lipoprotein metabolism 441 – disorders 217 – in dopamine β-hydroxylase defi- – pathway 440 218 ciency 413 Lipoprotein phenotypes 446 Ketone body ratio 25 LDL Lipoxygenase 213 Ketonuria 23 – binding and internalisation 443 Lipoxygenase activating protein 213 – degradation 443 Lissencephaly 6 – diagnostic approach 23, 24 LDLR 440 Liver cell transplantation Ketosphinganine 492 LDLR defect 448 – in urea cycle 308 Ketosphinganine reductase 492 L-dopa 262,412 Liver cysts 6 Ketotic hypoglycaemia 23, 24 – in dopa-responsive dystonia 415 Liver failure Kjers autosomal dominant optic – treatment in hydroxylase – diagnostic approach 21 atrophy 227 (TH) deficiency 412 – neonatal 10 Krabbe disease 57, 563 L-dopa-responsive dystonia 490 – emergency management 108 – screening 84 Lebers hereditary optic neuroretin- Liver glycogenoses 117 Krebs Cycle Disorders 197 opathy 227 Liver glycogen synthase 129 Kufs disease 571 Lec35 (Man-P-Dol utilisation 1) 611 Liver phosphorylase 129 Kuvan 255 Lecithin:cholesterol acyltransferase Liver transplantation (LCAT) 442 ,444 – in acute intermittent porphyria 525 – deficiency 453 – in bile acid defects 478 L Leigh’s disease/syndrome 227 ,59 – in GSD I 121 – in adults 60 – in GSD IV 124 Lesch-Nyhan syndrome 57, 508 – in familial 488 L-2-hydroxyglutarate 342 Lescol 456 – in methylmalonic/propionic aciduria – deficiency 342 90, 278 289 L-2-hydroxyglutaric aciduria 57 ,342 Leukoencephalopathies 66 – in maple syrup urine disease 286 142 – in adults 64 – in deficiency 129 – with ataxia 52 190 646 Subject Index

– in PKU 256 Lysosphingolipids 556 Medium-chain 3-ketoacyl-CoA thiolase – in tyrosinaemia type 1 270 Lysosulfatide 565 (MCKAT) deficiency 206 – in urea cycle 308 Medium-chain acyl-CoA dehydroge- L-malate dehydrogenase 342 nase 202 Long-chain 3-hydroxyacyl-CoA dehy- M – deficiency 205 drogenase 202 Medium-chain ketoacyl-CoA thiolase – deficiency 205 202 Long-chain acyl-CoA dehydrogenase Medium-chain (LCAD) deficiency 206 – diagnostic approach 37 – in fatty acid oxidation defects 211 Long-chain enoyl-CoA hydratase 202 Macrocytic anaemias 45 252 Long-chain ketoacyl-CoA thiolase 202 MELAS syndrome 227 Long-chain omega-3 polyunsaturated – diagnostic approach 52 Melibiose 145 fatty acids – neonatal 10 Membrane ghosts 602 – in PKU 257 Macrophage-activating syndrome Menine protein deficiency Long QT syndrome – diagnostic approach 49 – in pancreatic adenomas 170 – neonatal 10 Macrosomy 169 Menkes disease 539 Lorenzos oil 603 Macular cherry red spot 59 Mental retardation 456 MAD deficiency – diagnostic approach 27 Lovaza 458 – transient neonatal form 207 Mercaptopropionylglycine Low-density lipoprotein-like receptor metabolism 544 – in cystinuria treatment 366 440 – transport disorders 535 MERRF syndrome 227 Low-density-lipoprotein-lowering – treatment in primary hypo- Metabolic acidosis 12 456 magnesaemia 545 – diagnostic approach 23 Low-density lipoproteins (LDL) Malate 91 Metabolic acidosis – physical-chemical properties 441 Malate/aspartate shuttle 189 – diagnostic approach 22 Low-density lipoproteins (LDL) receptor Malate dehydrogenase 188 Metabolic distress 440 Maleylacetoacetate 266 – diagnostic approach 13 Low signal of basal ganglia 59 Malformations diagnostic approach 5 – neonatal 13 Lp(a) Malonic acid 92 Metabolic emergencies – physical-chemical properties 441 Malonic/Methyl malonic combined – diagnostic approach 15 L/P ratio 24 aciduria 293 Metabolic encephalopathy L-serine palmitoyltransferase 492 Malonic aciduria 293 – diagnostic approach 11 LTA4 hydrolase 213 Malonylcarnitine 293 Metabolic profiles 88 LTC4 synthase 213 Malonyl-CoA decarboxylase 278 – during fasting tests 97 LTC4 synthase deficiency 214 – deficiency 293 Metabolic samplings 100 Lupus like skin lesions 43 Mandelic 93 Metachromatic leukodystrophy 57, L-xylulose 153 Manganese metabolism 546 565 L-xylulose reductase 153 – transport disorders 535 Metalloporphyrin 520 Lymphadenopathy 22 Mannoheptulose 155 Metalloproteins 541 Lysine 90 Mannose-6-phosphate 609 Methenyltetrahydrofolate cyclohydro- – catabolic pathways 334 Mannose-phosphate isomerase 613 lase 394 – disorders 333 Mannosidosis 587 Methionine 90, 312 Lysine:2-oxoglutarate reductase 336 I, II, VI, VIII 609 Methionine S-adenosyltransferase 312 Lysine transcarbamoylase 324 Maple syrup urine disease 279 Methionine S-Adenosyltransferase Lysinuric protein intolerance 363, 366 – screening 82 Deficiency 317 Lysophosphatidic acid 487 Marfan syndrome 313 394 Lysosomal acid lipase deficiency Maroteaux-Lamy syndrome 582 ,585 Methionine synthase apoenzyme 393 447 Maternal PKU 258 Methionine synthase reductase 393 Lysosomal-associated membrane Maternal riboflavin deficiency 207 Methoxy-4-hydroxyphenylglycol 411 protein 2 132 Matriptase-2 Methoxytyrosine 419 Lysosomal storage disorders – deficiency 47 ,544 Methyl-3-hydroxybutyrate 282, 292, – screening 84 McArdle disease 127 93 647 Subject Index L–M

Methyl-3-hydroxybutyryl-CoA dehydro- Mevacor 456 Mitochondrial translation factors genase 278 Mevalonate 592 defects 231 – deficiency 292 462 Mitochondrial tyrosyl-tRNA synthetase Methylacetoacetyl-CoA thiolase 278 Mevalonate kinase deficiency 463 47 Methylacyl-CoA racemase 600 Mevalonate-P kinase 462 Mitochondrial uncoupling protein 2 – deficiency 597 Mevalonate-PP decarboxylase 462 – deficiency 169 Methylation cycle 312 Mevalonic 93 Mitofusin 2 231 Methyl branched-chain FAs 600 Mevalonic aciduria 463 MLASA syndrome 47, 227 Methylbutyryl-CoA 292 Mevalonolactone 93 MNGIE syndrome 227 Methylbutyryl-CoA dehydrogenase MGC-CoA hydratase 291 Molybdenum 312 deficiency 292 6 Molybdenum cofactor biosynthesis Methylcitrate 282 – diagnostic approach 37 507 Methylcobalamin 386 Microcornea Molybdenum cofactor deficiency Methylcobalamin Deficiency 393 – diagnostic approach 51 507 Methylcrotonic acid 290 Migalastat hydrochloride Molybdenum cofactor sulfurase 507 Methylcrotonyl-CoA carboxylase 278 – in Fabry disease 568 Monoamine metabolism 412 Methylcrotonylglycine 92, 290 Monoamine oxidase 411 Methylcrotonyl glycinuria 289, 290 – in Gaucher type I 559 Monoamine oxidase-A Deficiency Methylene tetrahydrofolate 350 – in Niemann-Pick type C 570 413 Methylenetetrahydrofolate reductase Miller Syndrome 512 Monocarboxylate transporter 1 394 Mitochondrial 3-hydroxy-3-methyl- – deficiency 169 – deficiency 396 glutaryl-CoA synthase deficiency Monocarboxylate transporter 8 44, Methylglutaconic 92 219 49 Methylglutaconic aciduria 291 ,489 Mitochondrial ADP/ATP translocator Monocarboxylic transporter 133 Methylglutaconic aciduria type I 57 230 Monohydroxy bile acids 480 Methylglutaconic aciduria Type I 291 Mitochondrial aspartate-glutamate acyltransferase Methylglutaconic aciduria Type II 489, carrier 298 487 291 – deficiency 31 Monolysocardiolipin acyltransferase-1 Methylglutaconic aciduria Type III 291 Mitochondrial assembly and stability 489 Methylglutaconic aciduria Type IV 291 230 Mono-neuropathy 65 Methylglutaconic aciduria Type V 291 Mitochondrial DNA (mtDNA) 228 Mononeuropathy, multiplex Methylglutaconyl-CoA hydratase 278 Mitochondrial DNA mutations 229 – in adults 64 Methylglutaric acids 291 Mitochondrial DNA rearrangements transporters 176 Methylmalonic acid 93,282 229 Morquio disease 582, 585 Methylmalonic aciduria 57, 279, 283, Mitochondrial fatty acid oxidation Mosaic islet cell hyperplasia 170 287 – pathway 202 Moth-eaten (HEM) skeletal dysplasia Methylmalonic semialdehyde dehy- Mitochondrial fatty acid oxidation 468 drogenase 278 202 Mouth ulcers Methylmalonyl-CoA epimerase 284 Mitochondrial fusion-fission defects – diagnostic approach 52 Methylmalonyl-CoA mutase 278, 392 231 Movement disorders 62 Methyl sterol oxidase 41 Mitochondrial genome 228 – in adults 61 Methyltetrahydrofolate 312, 394 Mitochondrial MPDU1-CDG (CDG-If) 611 Methyltetrahydrofolate-homocysteine defect 410 MPS IH 581 methyltransferase 312 Mitochondrial hsp60 chaperonopathy MPS IS 581 Methyl-THF 39 MSUD 57 – treatment in folate transport defects Mitochondrial nuclear DNA mutations MtDNA deletion 230 395 229 MtDNA depletion 230 Methyl THF-homocysteinemethyltrans- Mitochondrial nuclear genome 229 MtDNA γ 230 ferase 312 Mitochondrial and peroxisomal fission MtDNA stability defects 230 Methylthio-3-oxobutyrate 317 597 MTHFR deficiency 57 Metronidazole Mitochondrial ornithine transporter Mucolipidoses – in emergency management 107 298, 324 – classification 582 648 Subject Index

Mucolipidosis type I 587 N-acetylaspartic aciduria 345 Neuroimaging signs Mucolipidosis type II 587 N-acetylgalactosamine 556 – diagnostic approach 37 Mucolipidosis type III 587 N-acetylgalactosamine-4-sulfatase 582 Neurological deterioration Mucopolysaccharides 580 N-acetylgalactosamine-6-sulfatase 580 – diagnostic approach 7, 27 Mucopolysaccharidoses 579, N-acetylgalactosamine-6-sulfatase 582 – emergency management 105 581 N-acetylgalactosamine-6-sulfate – neonatal 7 – classification 582 sulfatase Neurological presentations in neonates 597, 601 – in GM1 gangliosidosis 561 – diagnostic approach 11 Multiple acyl-CoA dehydrogenase N-acetylglucosamine 586 Neurometabolic presentations (MAD) deficiency 206 N-acetyl-glucosamine-6-sulfatase – in adults 60 Multiple exostoses syndrome 610 582 Neuronal ceroid lipofuscinosis Multiple glycosylation pathways N-acetyl-glucosaminidase 582 – adult 571 – defects 611 N-acetylglutamate 301 – classic juvenile 571 Muscle-eye-brain disease 615 N-acetyl glutamate dehydrogenase – disorders 555 Muscle glycogenoses 127 deficiency 302 – infantile 571 Muscle glycogen synthase 129, 132 N-acetyl glutamate synthetase – late infantile 571 Muscle pain 19 298 Neuronal laforin/malin defects Myelopathy N-acetylneuraminic acid 556, 586 133 – acute 59 N-acetyltyrosine 93, 271 Neuro-ophthalmological signs – subacute 59 NAc-galactosamine 4-sulfatase – diagnostic approach 37 Myoadenylate deaminase 503 580 Neuropathy Myoclonia 32 NADH/NAD ratio 24 – acute 65 Myoclonic ataxia 70 NAD(P)-dependent steroid dehydro- – axonal 65 Myoclonic epilepsy genase-like 469 – demyelinating 65 – in adults 65 N-arachidonoylethanolamine 491 – dorsal root ganglis 65 Myoclonic epilepsy-ataxia-neuropathy NARP syndrome 227 – motoneurone 65 syndrome 33 NAT8L 346 – small fibres 65 Myoclonus Natowicz syndrome 585 Neurophysiological signs – diagnostic approach 33 N-carbamylglutamate 305 – diagnostic approach 40 Myoclonus 62 – in emergency management 107 Neurotransmission Myoglobinuria 19 Near-miss – disorders 405 – in adults 72 – diagnostic approach 18 Neurotransmitter defects 57 Myokinase 503 Necrosis of basal ganglia 59 Neurotransmitters Myoneurogastrointestinal encephal- Neonatal haemochromatosis 543 – classification 406 opathy 227 Neonatal hypoglycaemia Neutral amino acids Myopathy – emergency management 108 – transporter system 364 – cardiopathy 71 Neonatal period Neutral amino acid transporter – diagnostic approach 49 – diagnostic approach 6 364 – exercise intolerance and/or Nephrocalcinosis 75 myglobinuria 71 – diagnostic approach 50 N-glycans – in adults 70 Nephrolithiasis – synthesis 608 – progressive 49 – diagnostic approach 50 N-Glycans Myophosphorylase 129 Nephropathy (tubulo-interstitial) – synthesis 608 Myophosphorylase deficiency 127 – diagnostic approach 50 Niacin 440, 457 50 Niaspan 457 neural tube defects 6 Nicotinamide N – in Hartnup treatment 369 – in GM1 gangliosidosis 561 Nicotinamide adenine dinucleotide Neuraminidase 582 188, 202 NAA Neurodegeneration with Brain Iron Nicotinic acid 457 – N-acetylaspartate 345 accumulation 489, 543 Niemann-Pick disease N-Acetylaspartate 93 Neuroferritinopathy 544 – type A 559 649 Subject Index M–P

– type B 559 OH-butyryl-carnitine Ornithine transporter deficiency Niemann-Pick Disease Type C 57, 569 – in hyperinsulinism 170 302 Nifedipine O-glycans 608 Ornithine-δ-aminotransferase 324 – in hyperinsulinism 171 OH-isocaproic 92 Ornithine transcarbamoylase 298 269 OH-phenylacetic 93 Orotate phosphoribosyltransferase Nitric oxide 252 OH-phenyllactic 93 511 Nitric oxide synthase 252 OH-phenylpyruvic 93 Orotic 93 scavengers 305 OH-phytanoyl-CoA lyase 600 301 Nitroprusside test OH-sebacic 91 Orotic aciduria 512 – in cystinuria 365 583, 586 Orotidine 301, 512 NKH 57 Oligosaccharidoses 579, 587 Orotidine decarboxylase 511 NMDA receptor – classification 582 Orotidine monophosphate 511 – activation 353 Oligosaccharyltransferase 609 Orthostatic hypotension 21 NMR spectroscopy 95 Olivo-ponto-cerebellar signs Osteochondromas 614 Nodules – diagnostic approach 38 Osteopenia – diagnostic approach 43 O-mannosylglycan 609, 614 – diagnostic approach 51 Nonaka myopathy 615 O-mannosylglycan synthesis Osteoporosis Nonischaemic forearm exercise test – defects 610 – diagnostic approach 44 128 Omega-3 fatty acid Osteosarcomas 614 Non ketotic hypoglycaemia 26, 349 – in treatment of Osteosclerosis 467 Noradrenaline 458 Oxaloacetate 188 – metabolism 411 Omega-3 fish oil 440 Oxidosqualene sterol cyclase 462 Norbottnian Gaucher type III 558 O-N-acetylgalactosaminylglycans Oxo-3-CH3Val 92 414 609 Oxo- (or keto)acids 278 Northern epilepsy 572 O-N-acetylgalactosaminylglycan Oxoadipic Aciduria 337 Nova Scotia Niemann-Pick type D synthesis Oxoglutarate dehydrogenase complex 569 – defect 610 334 NTBC 269 Onco-metabolite 344 Oxo-isocaproic 92 Nucleotidase 500 Ophthalmoplegia Oxo-isovaleric 92 – diagnostic approach 40 oxoprolinase 424 Opisthotonus 9 Oxoprolinase deficiency 427 O Optic atrophy oxoproline 424 – diagnostic approach 40 Oxoprolinuria Optic nerve disorder 72, 73 – secondary 428 539 Optic neuropathy 59 O-xylosylglycans 609 Octacarboxyl porphyrin 521 Organic acid disorder O-xylosylglycan synthesis Octreotide – screening 83 – defects 610 – in hyperinsulinism 171 Organic acid O-xylosyl/N-acetylgalactosaminylglycan Ocular contraversion 40 – in fatty acid oxidation disorder synthesis Oculocutaneous Tyrosinaemia 271 209 – defect 610 Oculodentodigital syndromes 39 Ornithine 90, 358 Oxysterol 7α-hydroxylase 474 Odd-numbered long-chain fatty acids ornithine aminotransferase 358 Oxysterol 7α-Hydroxylase Deficiency 283 Ornithine aminotransferase deficiency 480 Oedema 325 – diagnostic approach 21 ornithine ketoacid transaminase 326 – neonatal 10 Ornithine metabolic pathways 324 P Oedema Ornithine metabolism 324 – diagnostic approach 21 – disorder 323 oedema of sun-exposed areas 22 Ornithine transcarbamoylase 298 P5-C dehydrogenase 358 O-fucosylglycans 609 Ornithine transcarbamoylase deficiency P5-C reductase 358 O-fucosylglycan synthesis 302 P5-C synthase 358 – defects 610 Ornithine transporter 298 Painful crisis 22 650 Subject Index

Pain in extremities Peroxisomal function 592 Phosphatidyl choline synthase 486 – diagnostic approach 22 Peroxisomal targeting signals 599 Phosphatidyl ethanolamine 487 Pallidum lesions 63 Peroxisomal β-oxidation 599 Phosphatidyl glycerol 487 Palmitoyl protein 1 biogenesis Phosphatidyl inositol 487 – deficiency 572 – disorders 597 Phosphatidyl serine 487 Pancreatic adenoma 169 – defects 58, 599 Phosphatidylserine decarboxylase 486 Pancreatic adenomas 170 Peroxisome proliferator-activated Phosphatidylserine synthase 486 Pancreatitis (acute) receptor coactivator-1α 488 8B – diagnostic approach 45 Peroxisome proliferator-activated – mutations 415 Pancytopenia receptor-α 488 Phosphoenolpyruvate 188 – diagnostic approach 47 Perseitol 155 Phosphoenolpyruvate carboxykinase 2 Personality changes 188 – deficiency 543 – in adults 69 – deficiency 191 Pantothenate Kinase-associated Neuro- Pes cavus 129 degeneration 490, 543 – in adults 64 – deficiency 128 Paradoxical hyperketonaemia 228 Petechiae 17 Phosphoglucomutase 129 Paraplegia 32 Peters plus syndrome 610 129 Parkinsonism/ Parkinson syndrome Phaeochromocytoma 229 – deficiency 128 34,62 PHARC Syndrome 490 Phosphoglycerate dehydrogenase – in adults 61 PHE hydroxylase 252 358 – infantile 412 Phenolic acids 271 – deficiency 360 Paroxysmal dyskinesia Phenylacetate/ Phenylacetic acid 93, 129 – in adults 64 253 – deficiency 130 Paroxysmal dystonia 62 Phenylacetylglutamine 305 Phosphoglycerides 487 – in adults 64 90 Phosphohydroxypyruvate transaminase Paroxysmal exertion-induced dystonia – metabolism 252 358 178 – teratogenic effects 258 A2 487 PDH deficiency 58 Phenylalanine ammonia lyase 256 Deficiency 489 PDHE1 kinase 191 Phenylalanine hydroxylase deficiency Phospholipase A2β 486 PDHE1 phosphatase 191 253 487 PDHE2 deficiency 192 Phenylalanine hydroxylation system Phospholipase Cγ 486 PDHE3-binding protein 252 Phospholipid biosynthesis 486 – E3BP 191 Phenylalanine (PHE) 252 Phospholipid synthesis 444 Pearson marrow-pancreas syndrome Phenylbutyrate 305 – disorders 485, 487 226 Phenylethylamine 414 Phospholipid transfer protein (PTP) 442 Pedalling movements 9 Phenylketones 253 Phosphomannomutase 2 609 Pelger-Huet anomaly 468 252 – deficiency 612 Pelizaeus-Merzbacher 39 – screening 82 Phosphomannose isomerase 609 Penicillamine Phenyllactate/ Phenyllactic acid 253, 93 – deficiency 613 – in Wilson disease 538 Phenylpyruvate/ Phenylpyruvic acid Phosphoribosyl pyrophosphate Pentose phosphate pathway 152 93, 253, 252 500,511 – disorders 151 Phosphatase 417, 487 Phosphoribosyl pyrophosphate Peptidase D 429 Phosphate 252 synthetase deficiency 502 Pericardial effusion 20 Phosphatidic acid 487 Phosphoribosyl pyrophosphate – neonatal 10 Phosphatidic acid cytidyltransferase synthetase superactivity 501 Perilipin deficiency 41 486, 487 Phosphorylase b-kinase deficiency 133 Peripheral neuropathies 32 Phosphatidic acid glycerol phosphate Phosphorylase kinase 129 – in adults 64 synthase 486, 487 – deficiency 125 Peritoneal dialysis Phosphatidic 486, Phosphorylcholine 556 – in emergency management 108 487 Phosphorylethanolamine 556 Peroxisomal disorders 591 – deficiency 487 aminotransferase – classification 597 Phosphatidyl choline 487 Deficiency 361 651 Subject Index P

Phosphoserine phosphatase 358 Posterior fossa abnormalities 6 Protoporphyrin 521 – deficiency 361 Posterior fossa signs Protoporphyrinogen oxidase 522 Phosphosphingolipids 556 – diagnostic approach 38 – deficiency 528 Photosensitivity Post-mortem Protocol 100 Proximal weakness in adults 72 – diagnostic approach 43 Postprandial hyperketonaemia 26 PRPP synthetase 500 Phytanic acid 480, 592, 598 Prader-Willi-like phenotype 10, Pseudodiabetes Phytanic acid α-oxidation 600 Pramipexole – diagnostic approach 44 Phytanoyl-CoA hydroxylase deficiency – in BH4 defects 262 Pseudodiabetic foot syndrome 493 597 Pravachol 456 Pseudo-Hurler 583,587 Pili torti 456 Pseudoscleroderma 526 – diagnostic approach 42 Pre-β-lipoproteins 441 Pseudo-stroke 61 Pipecolic acid 90, 334, 602 Primapterinuria 260 Pseudotumor cerebri 73 – in pyridoxine-dependent epilepsy Pristanal 600 Psoriasiform dermatitis 41 418 Pristanic acid 480, 598, 599 Psychiatric symptoms/ disorders 35 Pipecolic acid oxidase 334 Progressive ankylosis – diagnostic approach 17,18,27 PKU 252 – diagnostic approach 52 – in adults 66 – classic 254 Progressive cerebello-cerebral atrophy Psychosis (Acute) 17 – untreated 58 547 Psychosine 556, 564 Plasma amino acids Progressive external ophthalmoplegia Pterin-4a-carbinolamine 252 – variations 89 227 Pterin-4a-carbinolamine dehydratase Plasma apolipoproteins – in adults 72 252 – characteristics 441 Progressive myoclonic epilepsy 67 – deficiency 260 Plasmalogen 592, 598 Progressive neurological and mental Pterin-requiring enzymes 252 – biosynthesis defects 601 deterioration 29 Pterins 252 disturbances – diagnostic approach 32 – disorders 414 – diagnostic approach 47 – 1-12 months 30 Pteroylglutamic acid 394 Pneumopathy – 1-5 years 32 Ptosis – diagnostic approach 51 – 5-15 years 34 – diagnostic approach 40 – interstitial 51 Progressive sclerosing poliodystrophy Pulmonary hypertension Polarographic studies 227 – diagnostic approach 52 – in respiratory chain 232 429 Punctate epiphyseal calcifications Polycystic kidneys 6 90, 358 – diagnostic approach 51 – diagnostic approach 50 – disorders 357 Polycystic ovary 44 – synthesis 324 – pathways 500 Polyglucosan bodies 133 Proline oxidase 358 Purine metabolism Polymyoclonia 34 -deficiency 359 – disorders 499 – diagnostic approach 33 Prolonged QT interval 20 Purine Metabolism 500 Polyneuropathy 34 Propionic aciduria 58,279, 287 Purine phosphorylase – diagnostic approach 35, 41 Propionylcarnitine 282 500 – in adults 64 Propionyl-CoA carboxylase 278 – deficiency 506 Polyols 152 Propionylglycine 282 Purine cycle 503 Pompe disease 130 Prosaposin deficiency 568 Putamen lesions 63 POMT1 614 Protective protein/cathepsin A Pycnodysostosis 588 Porphobilinogen 521 – in GM1 gangliosidosis 561 Pyridoxal 5-phosphate 406, 411,417 – deficiency 524 Protein Loading Test 98 – therapeutic trial 420 Porphobilinogen deaminase 522 Protein N-glycosylation disorders 609 – disorders 417 – deficiency 524 Protein O-glycosylation disorders 610 Pyridoxal kinase 417 Porphyria 521 Protein X 191 -dependent – classification 522 – deficiency 192 glycine decarboxylase – laboratory tests for screening 523 Proteoglycans 580 – P-protein 352 Porphyria cutanea tarda 526,527 Protocol for emergency investigations Pyridox(am)ine 5-phosphate oxidase Postaxial acrofacial dysostosis 512 12 deficiency 419 652 Subject Index

Pyridox(am)ine phosphate oxidase 417 red blood cells disturbances S-adenosylhomocysteine 312 – deficiency 419 – diagnostic approach 45 S-adenosylhomocysteine hydrolase Pyridoxine Refsum disease 597 312 – disorders 417 – infantile 597 – deficiency 318 – treatment in homocystinuria 316 – classic 596 S-adenosylmethionine 312 – treatment in pyridoxine-responsive Rehydration SAICAR 502 epilepsy 419 – emergency management 105 583, 587 – treatment in OAT deficiency 327 Remodelling enzyme 487 Salt-losing syndrome 19 Pyridoxine-responsive Epilepsy 417 Renal glucosuria 178 – diagnostic approach 44 Pyrimethamine Renal transplantation Salt wasting 18 – treatment in chronic GM2 563 – in methylmalonic aciduria 289 Sandhoff disease 562 5’-nucleotidase 511 Renal tubular acidosis 582,585 – deficiency 514 – diagnostic approach 50 Santavuori-Haltia disease 571 Pyrimidine metabolism Respiratory alkalosis 13 Saposin 556 – pathways 511 Respiratory chain – deficiency 558 – disorders 499, 512 – defects 223 Saposin A deficiency 564 Pyroglutamic acid 93 – metabolic pathway 224 Saposine B deficiency 565 – see 5-oxoproline 425 Reticular dysgenesis 47, 504 Sapropterin dihydrochloride 255 Pyruvate carboxylase 188 Retinitis 72, 73 Sarco-/endo-plasmatic reticulum – deficiency 189 – diagnostic approach 40 (SERCA) ATPases 547 Pyruvate dehydrogenase complex 32, 33 SC4MOL gene 41 188,191 Reverse cholesterol transport 445 Scavenger class B type I receptor 442 – structure and activation/deactivation Reye syndrome – deficiency 453 system 191 – neonatal 10 Scavenger receptors – deficiency 192 – diagnostic 18 – CD 36 440 Pyruvate dehydrogenase phosphatase Rhizomelic chondrodysplasia punctata – class B type I 444 193 595, 597 – SR-A 440 Pyruvate metabolism 188 Ribitol 153, 155 Scheie disease 581, 582 – disorders 187 Riboflavin Schilling test 387 Pyruvate transporter defect 197 – in fatty acid oxidation defects 212 Schindler disease 583,587 Pyruvoyl-tetrahydropterin synthase – Riboflavin transport disorders 206 Schizophrenia 252, 411 – Riboflavin treatment in cerebral – in adults 68 Pyruvoyl-tetrahydropterin synthase organic acidurias 343 Schizophrenia-like episodes/ behaviour deficiency 260 Ribonucleotide reductase deficiency 17,18 231 Schneckenbecken dysplasia 610 153 Schwachman syndrome 47 Q Ribose-5-phosphate 153 SCO1/ SCO2 Mutation 230 Ribose-5-phosphate isomerase 152 Screening – deficiency 153 – metabolic markers 79 Q-dihydrobiopterin (qBH2) 252 Ribulose-5-phosphate 153 Second wind phenomenon 18. 127 Questran 457 Richner-Hanhart Syndrome 271 Sedoheptitol 155 Quinonoid dihydrobiopterin 411 Rickets 22 Sedoheptulokinase 152 Ring sideroblasts 521 – deficiency 153 RNASET2 deficiency 37 Sedoheptulose 155 R 456 Sedoheptulose-7-phosphate 154 Segawa disease / syndrome 412 Selegiline Raffinose 145 S – in BH4 defects 262 Ragged red fibres 227 Selenium Recurrent episodes of vomiting 17 – transport 535 Recurrent myoglobinuria dehydrogenase 336 – Metabolism 547 – diagnostic approach 18 336 Selenocysteine 547 653 Subject Index P–S

– disorders 547 Sitosterolaemia 450 SSADH deficiency 58 Selenoproteins 547 Sjögren-Larsson Syndrome 214 S-sulfocysteine 507 Self-mutilation 41 Skeletal malformations 5 Stachyose 145 Sensorineural deafness Skin rashes 43 Statins 456 – diagnostic approach 36 Skin ulcers 43 Status epilepticus Sensory defects 32 SLC6A8 deficiency 241 – in adults 66 Sepiapterin reductase 252, 411, 414 SLC17A5 39 Steatosis (Acute) – deficiency 415 Slow pre-β-lipoproteins 441 – neonatal 10 Serine 90, 312, 358 Sly syndrome 582,585 Sterol 27-hydroxylase 474 Serine deficiency 58 Smith-Lemli-Opitz syndrome 464 Sterol 27-hydroxylase deficiency 478 Serine Deficiency with ichthyosis and 305 Sterol C-4 demethylase complex 462, polyneuropathy 361 – in emergency management 107 466 Serine hydroxymethyl transferase 350, – in methylmalonic aciduria 287 Sterol-C4-methyl oxidase-like gene 358 – in propionic aciduria 287 defect 42 Serine metabolism – treatment in lysinuric protein Sterol C-14 demethylase 462 – disorders 357 intolerance 368 Stomatitis Serine palmitoyl CoA transferase 492 Sodium bicarbonate – diagnostic approach 52 – deficiency 361, 492, 493 – in emergency management 106 Strabismus Serine racemase 358 Sodium-dependent glucose trans- – diagnostic approach 40 Serine synthesis porters 176 Stridor – pathway 358 305 – diagnostic approach 52 252 – in emergency management 107 Stroke 61 – metabolism 411 – treatment in lysinuric protein – diagnostic approach 15 Serum carnosinase deficiency 428 intolerance 368 – in adults 61 Severe combined immunodeficiency Sorbitol 158 Stroke-like episodes 15 disease 504 Sorbitol dehydrogenase 158 Subdural haematoma 37 Severe combined immunodeficiency 32 – diagnostic approach 36 syndrome Spastic paraparesis 69 Suberylglycine 93 – screening 85 – in adults 69 Substrate reduction therapy Sexual ambiguity Spectrophotometric studies – in Gaucher disease 558 – diagnostic approach 44 – in respiratory chain 233 Succinate 91 SGLT1 deficiency 177 Spheroid bodies 489 – entry in the respiratory chain 224 SGLT2 deficiency 178 Sphinganine 492 Succinate-CoQ reductase 224 Short-/branched-chain acyl-CoA dehy- Sphingohydrolases 557 Succinate dehydrogenase 188 drogenase (SCAD) 202, 278 metabolism – deficiency 196 – deficiency 206,292 – disorders 555 Succinate-ubiquinone oxidoreductase Short-chain 3-hydroxyacyl-CoA dehy- Sphingolipid structure 556 196 drogenase (SCHAD) 202 Sphingomyelin 556 Succinic aciduria 293 – deficiency 169,206 Sphingomyelinase deficiencies Succinic semialdehyde dehydrogenase – in hyperinsulinism 170 (Sphingomyelinoses) 559 406 Sialic acid 556 Sphingosine 556 – deficiency 407 Sialic acid-containing glycosphingo- Spielmeyer-Vogt disease 571 Succinylacetoacetate 266 556 Spino-cerebellar ataxia 70 Succinylacetone 266, 93 Sialic acid transporter 583 59 Succinyladenosine 500 Sialidosis 587 Spondylocostal dysostosis type 3 Succinylaminoimidazolecarboxamide Sialidosis I 582 610 ribotide 500 Sialidosis type 1 58 Spot test Succinyl-carnitine 284 Sialotransferrin 612 – in galactosaemia 144 Succinyl-CoA 3-oxoacid CoA transferase Sialyltransferase-9 492 SPTAN1 encoding β-II spectrin 39 188,218, Sideroblastic anaemias 45 Squalene 462 – deficiency 219 Simvastatin 456 Squalene epoxidase 462 Succinyl-CoA synthase 283 301 Squalene synthase 462 – deficiency 231 654 Subject Index

SUCLA2 231 TG transport protein Transient asymptomatic jaundice – deficiency 284 – microsomal 440 – neonatal 10 SUCLG1 231 Thalamus lesions 63 Transketolase 154 – deficiency 284 Thiamine Translocase Deficiency 117 -isomaltase deficiency 161 – in PDH deficiency 194 Trans-sulfuration pathway 312 158 Thiamine pyrophosphate 191 Treadmill test 99 Sudden unexpected Death in infancy Thiamine transporter hTHTR2 379 Tricarboxylic acid cycle 188 – diagnostic approach 18 Thiamine transporter (SLC19A3) – disorders 187 Sulfate 312 mutations 58 Trichorrhesis nodosa 300 Sulfatide 492, 556, 565 Thioester-homocysteine-thiolactone – diagnostic approach 42 Sulfite 312 314 Trientine Sulfite oxidase 312 Thiolases 600 – in Wilson disease 538 – deficiency 319, 507 Thiopurine methyltransferase Trifunctional protein (MTP) 202 Sulfocysteine 90 Deficiency 509 – deficiency 205 Sulfogalactosyltransferase 492 Thiosulfate 507 Triglyceride-lowering drugs 458 Sulfonylurea-receptor 90 440 – defects 169 Thrombocytopenia Sulfonylurea receptor (SUR1) 168 – diagnostic approach 47 – in pyruvate carboxylase deficiency Sulfur amino acid metabolism Thrombosis 59 190 – disorders 311 Thymidine 511 – in fatty acid oxidation defects 211 Sulfur-containing amino acids 511 Trihydroxycholestanoic acid 592,598, – metabolism 312 – deficiency 515,230 599 Supranuclear gaze palsy 59 Thymidine monophosphate 511 Trihydroxycoprostanic acid 480 SURF1 Mutation 230 Thymidine phosphorylase 511 Trimethylamine Sweating disturbances 22 Thymidine phosphorylase deficiency – metabolism 432 Syncope 20 231, 514 431 Systemic iron overload syndromes Thymidylate 394 – secondary 433 542 Thymine 93, 513 – transient 433 Tiglic acid 282 Triokinase 158 Tiglylglycine 282, 292 Tripeptidyl peptidase I T TMA N-oxide 432 – deficiency 572 TMEM70 mutation 230 Trometamol Total parenteral nutrition – in emergency management 109 TACH 39 – in emergency management 106 Tryptophan Tafazzin 489 Toulouse-Lautrec disability 588 – catabolic pathways 334 559 Transaldolase 152 Tryptophan hydroxylase 252 Tamponade 20 – deficiency 153 Tubulopathy Tangier disease 453 Transaminases (Elevated) – diagnostic approach 50 Tarui disease 128 – in neonates 10 Twinkle helicase 230 Taurine 90 Transcinnamic acid 256 Tyramine 271 Taurine-conjugated bile acids 477, Transcobalamin 386 Tyrosinaemia type I 267 482 – deficiency 388 – screening 83 Tay-Sachs disease 562 Transcobalamin Receptor Deficiency – transient 273 Telangiectasias – purpuras – petechiae 389 Tyrosinaemia type II 271 – diagnostic approach 43 Transferase 582 Tyrosinaemia Type III 272 Tetracarboxyl porphyrin 521 Transferrin 541 Tyrosine 90 (BH4) 252, 411 – in hereditary fructose intolerance Tyrosine aminotransferase 266 – disorders 260 162 – cytosolic 271 Tetrahydrofolate 394 – isoelectrofocusing patterns 612 Tyrosine hydroxylase 252, 411 Tetrahydrofolate-requiring amino- – isoelectrofocusing of serum 610 – deficiency 412 methyltransferase Transferrin receptor 2 541 Tyrosine metabolism 266 – T-protein 352 – deficiency 543 – disorders 265 655 Subject Index S–X

Urine pH 12 Vitamin Therapy U Uronic acid 580 – in emergency management 107 Uroporphomethene 527 VLDL Ubidecarenone 235 Uroporphyrin 521 – biosynthesis 442 Ubiquinone deficiencies 230 Uroporphyrinogen decarboxylase – secretion and metabolism 443 UDPgalactose 142 – deficiency 527, 528 Vomiting (Chronic) – in the synthesis of glycoconjugates Uroporphyrinogen decarboxylase – diagnostic approach 44 142 522 Vomiting with lethargy UDPgalactose-4-epimerase 142 Uroporphyrinogen III cosynthase – diagnostic approach 16 UDP-GlcNAc epimerase/kinase 611 – deficiency 526 Vytorin 457 UDPglucose 142 Uroporphyrinogen III cosynthase UDPglucose pyrophosphorylase 142 522 UDP-N-acetylgalactosamine 142 Uroporphyrinogen I synthase W Ulceration 43 – deficiency 524 UMP synthase 511 Ursodeoxycholic acid UMP Synthase Deficiency 512 – in bile acid defects 478 Walker-Warburg Syndrome 614 Uncooked corn starch Usher syndrome type II 31 Welchol 457 – in GLUT2 deficiency 181 White blood cells disturbances – in glycogenosis 119 – diagnostic approach 47 – in ketotic hypoglycaemia 24 V White matter hyperintensity Uncoordinated movements 32 – diagnostic approach 39 Unesterified cholesterol Wilson Disease 58,537 – in Niemann-Pick type A/B 560 VACTERL association 226 Wolff-Parkinson-White syndrome Unsaturated fatty acids Vacuolated 133 – oxidation 202 – diagnostic approach 47 Wolfram syndrome 227 Unsteady gait 32 90, 278 Wolman disease 447 Uracil 93, 513 Vanillactic 93 Wrinkly skin syndrome 615 Urea cycle Vanillylmandelic acid 411 – metabolic pathway 298 Vanilpyruvic 93 – screening 82 Variegate porphyria 528 X – disorders 297 559 Ureidopropionase 511 Ventricular tachycardia 21 Ureidopropionase deficiency 514 – neonatal 10 Xanthelasma 454 Uric acid 500 Very-long-chain acyl-CoA dehydroge- Xanthine dehydrogenase 506 Uric acid to creatinine nase 202 Xanthine oxidase 500 – ratio 508 – deficiency 205 – deficiency 506 – diagnostic approach Very-long-chain fatty acid 592,598, Xanthine oxidoreductase 506 – diagnostic approach 599 – type I/ type II 506 Uridine 511 Very low-density lipoproteins (VLDL) Xanthoma – treatment in hereditary orotic 440 – diagnostic approach 43 aciduria 512 Vesicular ATPase Xanthomata 59 Uridine diphosphate galactose 142 – defects 611 Xanthosine monophosphate 500 Uridine diphosphate galactose Vesiculous bullous lesions X-linked adrenoleukodystrophy 4-epimerase deficiency 147 – diagnostic approach 43 596 Uridine diphosphate glucose 492, 608 Vigabatrin 408 X-linked distal hereditary motor Uridine diphosphate N-acetyl- Visceral aplasia 6 neuropathy 539 glucosamine 608 Visual hallucinations X-linked dominant chondrodysplasia Uridine diphospho-N-acetyl- – in adults 69 punctata 2 465 glucosamine epimerase/N-acetyl- Visual problems 72 X-linked sideroblastic anaemia 521 mannosamine kinase 615 417 Xylitol 153 Uridine kinase 511 Vitamin B12 Xylitol dehydrogenase 153 Uridine monophosphate 511 – in Methylmalonic Aciduria 288 Xylulose-5-phosphate 153 656 Subject Index

Z

Zellweger syndrome 594,597 Zinc – transport disorders 535 – treatment in Wilson disease 538 – in acrodermatitis enteropathica 549 Zinc deficiency in breastfed babies 549 Zinc-finger proteins 548 Zinc metabolism 548 Zinc therapy 549 Zinc transporters 548 Zocor 456 Printing and Binding: Stürtz GmbH, Würzburg