Biotinidase Deficiency: “If You Have to Have an Inherited Metabolic

Total Page:16

File Type:pdf, Size:1020Kb

Biotinidase Deficiency: “If You Have to Have an Inherited Metabolic ©American College of Medical Genetics and Genomics GENETEST REVIEW Biotinidase deficiency: “if you have to have an inherited metabolic disease, this is the one to have” Barry Wolf, MD, PhD1,2 Biotinidase recycles the vitamin biotin. Biotinidase deficiency is an about the natural history of the disorder. Regardless, the disorder is autosomal recessively inherited neurocutaneous disorder. The symp- an ideal example of an inherited metabolic disorder that if untreated toms of the disorder can be successfully treated or prevented by can result in major disabilities, but if identified early can be readily administering pharmacological doses of biotin. The biotinidase gene treated by the oral administration of a vitamin. (BTD) has been cloned and sequenced; its genomic organization has Genet Med 2012:14(6):565–575 been determined and more than 150 mutations have been identified. The disorder meets the major criteria for newborn screening and is Key Words: biotin; biotinidase; biotinidase deficiency; carboxylase being universally adopted in the United States and in many countries deficiency; mutation analysis; newborn screening around the world. Newborn screening will limit our understanding INTRODUCTION purified to homogeneity from plasma.3,10,11 Normal serum Biotinidase (E.C. 3.5.1.12) is the enzyme that recycles the vita- or plasma biotinidase is a monomeric sialylated glycopro- min biotin.1,2 As a vitamin, biotin comes from the diet either in tein with a molecular mass of 76–77 kDa. The enzyme has at the free, non-protein-bound form or as small biotinylated pep- least nine isoforms (four major and five minor) between pH tides bound to protein.3 Biotin in the free form can directly enter 4.15 and 4.35 as observed by isoelectric focusing.12 It has six the biotin pool and be used by the four carboxylases that use it putative N-linked glycosylation sites (arginine-X-threonine/ to convert them from the inactive to the active forms.4 The car- serine). Glycosylation of the protein could increase its mass boxylases propionyl-CoA carboxylase and β-methylcrotonyl- by 13 to 19 kDa; the molecular mass of the glycosylated CoA carboxylase are important for protein catabolism, ­pyruvate enzyme is estimated to be between 70 and 76 kDa, which carboxylase is essential for gluconeogeneis, and acetyl CoA car- is consistent with that of the reported glycosylated serum boxylase is the first step in fatty acid synthesis.5 Protein-bound enzyme.3,10,11,13 Most of the microheterogeneity observed on biotin must be proteolytically degraded to release biocytin isoelectric focusing results from differences in the degree of (biotinyl-ε-lysine) and/or small biotinyl-peptides that can be sialylation. further cleaved by biotinidase, releasing the free biotin to enter Biotinidase is a thiol enzyme that migrates to the α1-region on the pool.3 A major function of biotinidase is to recycle biotin agarose electrophoresis. The serum enzyme has a pH optimum liberated from biocytin and/or small biotinyl-peptides from of 5–6 when biocytin or biotinyl-p-aminobenzoate (artificial degraded holocarboxylases. substrate) is the substrate.1,3,11 Biocytin is cleaved more readily Biotinidase deficiency (OMIM# 253260 and 609019), the than larger biotinyl-peptides.3 Biotinidase apparently does not major cause of late-onset biotin-responsive multiple carboxylase cleave biotin from intact holocarboxylases. The biotinyl-binding deficiency, is an autosomal recessively inherited neurocutane- site of biotinidase is specific for the ureido group of the biotinyl ous disorder.2,6,7 The symptoms of the disorder can be success- moiety of various substrates.11,14 Biotinidase plays a role in the fully treated or prevented by administering pharmacological processing of dietary protein-bound biotin7,15 and has been doses of biotin. Newborn screening of the disorder is performed shown to transfer biotin from biocytin to nucleophiles, such as in most states and many countries. Frequently asked questions histones16; the physiologic significance of the latter activity is by parents and health-care providers and various issues about not known. biotinidase deficiency have been addressed in a recent paper.8 The three-dimensional structure of the majority of the enzyme has been predicted through its homology with nitrilases and THE ENZYME amidases from microorganisms.17 The active site of the enzyme Biotinidase has been shown to have biotinyl-hydrolase and involved in the cleavage of the amide bond of biocytin is simi- biotinyl-transferase activities.9 Human biotinidase has been lar in all the enzymes. The portion of the enzyme that is not 1Department of Medical Genetics, Henry Ford Hospital, Detroit, Michigan, USA; 2Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USA. Correspondence: Barry Wolf ([email protected]) Submitted 1 August 2011; accepted 6 September 2011; advance online publication 5 January 2012. doi:10.1038/gim.2011.6 GENETICS in MEDICINE | Volume 14 | Number 6 | June 2012 565 GENETEST REVIEW WOLF | Biotinidase deficiency predicted by the modeling is likely important for binding the which contains the N-terminal methionine of the mature biotinyl moiety of biocytin. enzyme. The presence of an intron between the two possible initiation codons could allow for alternative splicing, which Biotinyl-hydrolase activity could produce transcripts encoding a protein with a 41- or a Polyclonal and monoclonal antibodies prepared against puri- 21-residue signal peptide.23 fied human biotinidase react on immunoblot with biotinidase The nucleotide sequence upstream of exons 1 and 2 has been in extracts of normal fibroblasts and lymphoblasts.9 These examined for putative promoter elements. Promoter features antibodies react with normal serum biotinidase that has been identified from −600 to +400 are consistent with the ubiqui- desialylated by treatment with neuraminidase. Individuals with tous expression of biotinidase with characteristics of a CpG profound biotinidase deficiency can be classified into at least island, lack of a TATA element, six consensus methylation sites, nine distinct biochemical phenotypes on the basis of the pres- and three initiator (Inr) sequences, which are thought to be ence or absence of cross-reacting material (CRM) to biotini- important in transcription initiation of TATA-less promoters. dase, the number of isoforms, and the distribution frequency of A consensus sequence for the liver-specific transcription factor the isoforms.18 The isoform patterns observed in the individu- HNF-5 is present at −352. The nucleotide sequence 5′ of exon 2, als with partial biotinidase deficiency were not different from which contains the second putative ATG initiation codon, has those of individuals with profound biotinidase deficiency who features associated with housekeeping genes but does contain had CRM. a consensus sequence for the liver-specific transcription factor C/EBP within 300 bp of the 5′ end of exon 2. Biotinyl-transferase activity More than 100 children with profound biotinidase deficiency CLINICAL FEATURES OF BIOTINIDASE have been assessed for biotinyl-transferase activity and the pres- DEFICIENCY ence of CRM to antibodies prepared against purified serum bio- Clinically, children with profound biotinidase deficiency, if tinidase.16 Sera from all the symptomatic individuals studied— untreated, usually exhibit one or more of the following symp- both CRM-negative and CRM-positive—had no biotinyl- toms: hypotonia; seizures; eczematous skin rash; alopecia; respi- transferase activity. Sera from children detected by newborn ratory problems, such as hyperventilation, laryngeal stridor, and screening who were CRM-negative had no biotinyl-transferase apnea; conjunctivitis, candidiasis; ataxia; developmental delay; activity, whereas a considerable number of the CRM-positive hearing loss; and vision problems, such as optic atrophy.2,24 children had varying degrees of transferase activity. There was a Metabolically, most untreated individuals with biotinidase statistically significant difference in biotinyl-transferase activity deficiency will have one or more of the following: ketolactic aci- between the population of symptomatic enzyme-deficient chil- dosis, organic aciduria, and mild hyperammonemia.24,25 How- dren and those children who were identified by newborn screen- ever, the absence of organic aciduria or metabolic ketoacidosis ing. There was also a difference in the biotinyl-hydrolase activity does not exclude the diagnosis of biotinidase deficiency in a between the symptomatic and newborn screening group.19 symptomatic child. Symptoms of untreated profound biotinidase deficiency usu- MOLECULAR ORGANIZATION AND ally appear between the ages of 1 week and 10 years, with a mean CHARACTERIZATION OF THE BIOTINIDASE GENE age of 3.5 months.25 Some children with biotinidase deficiency The gene for human biotinidase (BTD) is located on chromo- exhibit only a single symptom, whereas others have multiple some 3q25.20 The complementary DNA (cDNA) for human neurological, cutaneous, or biochemical findings. biotinidase from a human cDNA hepatic library has two The most common neurologic features of individuals with putative ATG initiation codons and an open reading frame of untreated, profound biotinidase deficiency are seizures and 1,629 bp, relative to the first ATG codon.21 The cDNA encodes hypotonia.2,6,25–27 The seizures are usually myoclonic, but may for a mature protein of 543 amino acids with a molecular mass be grand mal and focal; some children
Recommended publications
  • Ovulation-Selective Genes: the Generation and Characterization of an Ovulatory-Selective Cdna Library
    531 Ovulation-selective genes: the generation and characterization of an ovulatory-selective cDNA library A Hourvitz1,2*, E Gershon2*, J D Hennebold1, S Elizur2, E Maman2, C Brendle1, E Y Adashi1 and N Dekel2 1Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA 2Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel (Requests for offprints should be addressed to N Dekel; Email: [email protected]) *(A Hourvitz and E Gershon contributed equally to this paper) (J D Hennebold is now at Division of Reproductive Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006, USA) Abstract Ovulation-selective/specific genes, that is, genes prefer- (FAE-1) homolog, found to be localized to the inner entially or exclusively expressed during the ovulatory periantral granulosa and to the cumulus granulosa cells of process, have been the subject of growing interest. We antral follicles. The FAE-1 gene is a -ketoacyl-CoA report herein studies on the use of suppression subtractive synthase belonging to the fatty acid elongase (ELO) hybridization (SSH) to construct a ‘forward’ ovulation- family, which catalyzes the initial step of very long-chain selective/specific cDNA library. In toto, 485 clones were fatty acid synthesis. All in all, the present study accom- sequenced and analyzed for homology to known genes plished systematic identification of those hormonally with the basic local alignment tool (BLAST). Of those, regulated genes that are expressed in the ovary in an 252 were determined to be nonredundant.
    [Show full text]
  • Mapping Influenza-Induced Posttranslational Modifications On
    viruses Article Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells Svetlana Rezinciuc 1, Zhixin Tian 2, Si Wu 2, Shawna Hengel 2, Ljiljana Pasa-Tolic 2 and Heather S. Smallwood 1,3,* 1 Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA; [email protected] 2 Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA; [email protected] (Z.T.); [email protected] (S.W.); [email protected] (S.H.); [email protected] (L.P.-T.) 3 Children’s Foundation Research Institute, Memphis, TN 38105, USA * Correspondence: [email protected]; Tel.: +1-(901)-448–3068 Academic Editor: Italo Tempera Received: 10 October 2020; Accepted: 2 December 2020; Published: 8 December 2020 Abstract: T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) to histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis by MS can detect species missed by bottom-up approaches. We used a novel approach of online two-dimensional liquid chromatography-tandem MS with high-resolution reversed-phase liquid chromatography (RPLC), alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. The first online RPLC separation sorted histone families, then RPLC or weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative identifications were assigned by matching proteoform masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for histone-intact protein PTM mapping (HiPTMap) to identify and quantify proteoforms purified from CD8 T cells after in vivo influenza infection.
    [Show full text]
  • Supplement 1 Overview of Dystonia Genes
    Supplement 1 Overview of genes that may cause dystonia in children and adolescents Gene (OMIM) Disease name/phenotype Mode of inheritance 1: (Formerly called) Primary dystonias (DYTs): TOR1A (605204) DYT1: Early-onset generalized AD primary torsion dystonia (PTD) TUBB4A (602662) DYT4: Whispering dystonia AD GCH1 (600225) DYT5: GTP-cyclohydrolase 1 AD deficiency THAP1 (609520) DYT6: Adolescent onset torsion AD dystonia, mixed type PNKD/MR1 (609023) DYT8: Paroxysmal non- AD kinesigenic dyskinesia SLC2A1 (138140) DYT9/18: Paroxysmal choreoathetosis with episodic AD ataxia and spasticity/GLUT1 deficiency syndrome-1 PRRT2 (614386) DYT10: Paroxysmal kinesigenic AD dyskinesia SGCE (604149) DYT11: Myoclonus-dystonia AD ATP1A3 (182350) DYT12: Rapid-onset dystonia AD parkinsonism PRKRA (603424) DYT16: Young-onset dystonia AR parkinsonism ANO3 (610110) DYT24: Primary focal dystonia AD GNAL (139312) DYT25: Primary torsion dystonia AD 2: Inborn errors of metabolism: GCDH (608801) Glutaric aciduria type 1 AR PCCA (232000) Propionic aciduria AR PCCB (232050) Propionic aciduria AR MUT (609058) Methylmalonic aciduria AR MMAA (607481) Cobalamin A deficiency AR MMAB (607568) Cobalamin B deficiency AR MMACHC (609831) Cobalamin C deficiency AR C2orf25 (611935) Cobalamin D deficiency AR MTRR (602568) Cobalamin E deficiency AR LMBRD1 (612625) Cobalamin F deficiency AR MTR (156570) Cobalamin G deficiency AR CBS (613381) Homocysteinuria AR PCBD (126090) Hyperphelaninemia variant D AR TH (191290) Tyrosine hydroxylase deficiency AR SPR (182125) Sepiaterine reductase
    [Show full text]
  • Counsyl Foresight™ Carrier Screen Disease List
    COUNSYL FORESIGHT™ CARRIER SCREEN DISEASE LIST The Counsyl Foresight Carrier Screen focuses on serious, clinically-actionable, and prevalent conditions to ensure you are providing meaningful information to your patients. 11-Beta-Hydroxylase- Bardet-Biedl Syndrome, Congenital Disorder of Galactokinase Deficiency Deficient Congenital Adrenal BBS1-Related (BBS1) Glycosylation, Type Ic (ALG6) (GALK1) Hyperplasia (CYP11B1) Bardet-Biedl Syndrome, Congenital Finnish Nephrosis Galactosemia (GALT ) 21-Hydroxylase-Deficient BBS10-Related (BBS10) (NPHS1) Gamma-Sarcoglycanopathy Congenital Adrenal Bardet-Biedl Syndrome, Costeff Optic Atrophy (SGCG) Hyperplasia (CYP21A2)* BBS12-Related (BBS12) Syndrome (OPA3) Gaucher Disease (GBA)* 6-Pyruvoyl-Tetrahydropterin Bardet-Biedl Syndrome, Cystic Fibrosis GJB2-Related DFNB1 Synthase Deficiency (PTS) BBS2-Related (BBS2) (CFTR) Nonsyndromic Hearing Loss ABCC8-Related Beta-Sarcoglycanopathy and Deafness (including two Cystinosis (CTNS) Hyperinsulinism (ABCC8) (including Limb-Girdle GJB6 deletions) (GJB2) Muscular Dystrophy, Type 2E) D-Bifunctional Protein Adenosine Deaminase GLB1-Related Disorders (SGCB) Deficiency (HSD17B4) Deficiency (ADA) (GLB1) Biotinidase Deficiency (BTD) Delta-Sarcoglycanopathy Adrenoleukodystrophy: GLDC-Related Glycine (SGCD) X-Linked (ABCD1) Bloom Syndrome (BLM) Encephalopathy (GLDC) Alpha Thalassemia (HBA1/ Calpainopathy (CAPN3) Dysferlinopathy (DYSF) Glutaric Acidemia, Type 1 HBA2)* Canavan Disease Dystrophinopathies (including (GCDH) (ASPA) Alpha-Mannosidosis Duchenne/Becker Muscular
    [Show full text]
  • Child Neurology: Hereditary Spastic Paraplegia in Children S.T
    RESIDENT & FELLOW SECTION Child Neurology: Section Editor Hereditary spastic paraplegia in children Mitchell S.V. Elkind, MD, MS S.T. de Bot, MD Because the medical literature on hereditary spastic clinical feature is progressive lower limb spasticity B.P.C. van de paraplegia (HSP) is dominated by descriptions of secondary to pyramidal tract dysfunction. HSP is Warrenburg, MD, adult case series, there is less emphasis on the genetic classified as pure if neurologic signs are limited to the PhD evaluation in suspected pediatric cases of HSP. The lower limbs (although urinary urgency and mild im- H.P.H. Kremer, differential diagnosis of progressive spastic paraplegia pairment of vibration perception in the distal lower MD, PhD strongly depends on the age at onset, as well as the ac- extremities may occur). In contrast, complicated M.A.A.P. Willemsen, companying clinical features, possible abnormalities on forms of HSP display additional neurologic and MRI abnormalities such as ataxia, more significant periph- MD, PhD MRI, and family history. In order to develop a rational eral neuropathy, mental retardation, or a thin corpus diagnostic strategy for pediatric HSP cases, we per- callosum. HSP may be inherited as an autosomal formed a literature search focusing on presenting signs Address correspondence and dominant, autosomal recessive, or X-linked disease. reprint requests to Dr. S.T. de and symptoms, age at onset, and genotype. We present Over 40 loci and nearly 20 genes have already been Bot, Radboud University a case of a young boy with a REEP1 (SPG31) mutation. Nijmegen Medical Centre, identified.1 Autosomal dominant transmission is ob- Department of Neurology, PO served in 70% to 80% of all cases and typically re- Box 9101, 6500 HB, Nijmegen, CASE REPORT A 4-year-old boy presented with 2 the Netherlands progressive walking difficulties from the time he sults in pure HSP.
    [Show full text]
  • Nutrition 102 – Class 3
    Nutrition 102 – Class 3 Angel Woolever, RD, CD 1 Nutrition 102 “Introduction to Human Nutrition” second edition Edited by Michael J. Gibney, Susan A. Lanham-New, Aedin Cassidy, and Hester H. Vorster May be purchased online but is not required for the class. 2 Technical Difficulties Contact: Erin Deichman 574.753.1706 [email protected] 3 Questions You may raise your hand and type your question. All questions will be answered at the end of the webinar to save time. 4 Review from Last Week Vitamins E, K, and C What it is Source Function Requirement Absorption Deficiency Toxicity Non-essential compounds Bioflavonoids: Carnitine, Choline, Inositol, Taurine, and Ubiquinone Phytoceuticals 5 Priorities for Today’s Session B Vitamins What they are Source Function Requirement Absorption Deficiency Toxicity 6 7 What Is Vitamin B1 First B Vitamin to be discovered 8 Vitamin B1 Sources Pork – rich source Potatoes Whole-grain cereals Meat Fish 9 Functions of Vitamin B1 Converts carbohydrates into glucose for energy metabolism Strengthens immune system Improves body’s ability to withstand stressful conditions 10 Thiamine Requirements Groups: RDA (mg/day): Infants 0.4 Children 0.7-1.2 Males 1.5 Females 1 Pregnancy 2 Lactation 2 11 Thiamine Absorption Absorbed in the duodenum and proximal jejunum Alcoholics are especially susceptible to thiamine deficiency Excreted in urine, diuresis, and sweat Little storage of thiamine in the body 12 Barriers to Thiamine Absorption Lost into cooking water Unstable to light Exposure to sunlight Destroyed
    [Show full text]
  • TITLE: Biotinidase Deficiency PRESENTER: Anna Scott Slide 1
    TITLE: Biotinidase Deficiency PRESENTER: Anna Scott Slide 1: Hello, my name is Anna Scott. I am a biochemical genetics laboratory director at Seattle Children’s Hospital. Welcome to this Pearl of Laboratory Medicine on “Biotinidase Deficiency.” Slide 2: Lecture Overview For today’s Pearl, I will start with background information about biotinidase including its role in metabolism and clinical features. Then we will discuss different clinical assays that can detect and diagnose the enzyme deficiency. Finally, I will touch on biotinidase as it relates to newborn screening. Slide 3: Background Biotinidase deficiency is an inborn error of metabolism, specifically affecting biotin metabolism. Biotin is also known as vitamin B7. Most free biotin is absorbed through the gut from food. This vitamin is an essential cofactor for four carboxylase enzymes. Biotin metabolism primarily consists of two steps- 1) loading the free biotin into an apocarboxylase to form the active form of the enzyme, called holocarboylases and 2) recycling biocytin back to lysine and free biotin after protein degradation. The enzyme responsible for loading free biotin into new enzymes is holocarboxylase synthetase. Loss of function of this enzyme can cause clinical features similar to biotinidase deficiency, typically with an earlier age of onset and greater severity. Biotinidase deficiency results in failure to recycle biocytin back to free biotin for re-incorporation into a new apoenzyme. Slide 4: Clinical Symptoms and Therapy © 2016 Clinical Chemistry Pearls of Laboratory Medicine Title Classical clinical symptoms associated with biotinidase deficiency include: alopecia, eczema, hearing and/or vision loss, and acidosis. During acute illness, hyperammonemia, seizures, and coma can also manifest.
    [Show full text]
  • Biotinidase Deficiency: a Survey of 10 Cases
    Arch Dis Child: first published as 10.1136/adc.63.10.1244 on 1 October 1988. Downloaded from Archives of Disease in Childhood, 1988, 63, 1244-1249 Biotinidase deficiency: a survey of 10 cases H J WASTELL,* K BARTLET,t G DALE,* AND A SHEIN *Department of Clinical Biochemistry, Newcastle General Hospital, and tDepartments of Child Health and Clinical Biochemistry, Newcastle University Medical School, Newcastle upon Tyne SUMMARY Ten patients with biotinidase deficiency were studied. Clinical findings at presenta- tion varied with dermatological signs (dermatitis and alopecia), neurological abnormalities (fits, hypotonia, and ataxia), and recurrent infections being the most common features, although none of these occurred in every case. Biochemically the disease is characterised by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia, and mental retardation. The cause of this permanent damage remains obscure and it is not clear if the early introduction of treatment will prevent it. Biotin is a cofactor required by acetyl CoA carboxy- a functional biotin deficiency (biotinidase deficiency) lase (ACC) [EC 6.4.1.2], pyruvate carboxylase (PC) caused by failure to recycle endogenous biotin and [EC 6.4.1.1], propionyl CoA carboxylase (PCC) to liberate dietary biotin, or by defective biotinylation copyright. [EC 6.4.1.3] and 3 methylcrotonyl CoA carboxylase of apocarboxylase because of a mutant holocarboxy- (MCC) [EC 6.4.1.4.].' It is covalently attached to lase synthetase that has an increased Km with the apocarboxylases by the epsilon amino group of a respect to biotin.
    [Show full text]
  • Bone Disorder and Reduction of Ascorbic Acid Concentration Induced by Biotin Deficiency in Osteogenic Disorder Rats Unable to Synthesize Ascorbic Acid
    J. Clin. Biochem. Nutr., 12, 171-182, 1992 Bone Disorder and Reduction of Ascorbic Acid Concentration Induced by Biotin Deficiency in Osteogenic Disorder Rats Unable to Synthesize Ascorbic Acid Yuji FURUKAWA,1,* Akiko KINOSHITA,1,•õ1 Hiroichi SATOH,1,•õ2 Hiroko KIKUCHI,1, •õ3 Shoko OHKOSHI,1,•õ4 Masaru MAEBASHI,2 Yoshio MAKINO,3 Takao SATO,4 Michiko ITO,1 and Shuichi KIMURA1 1 Laboratory of Nutrition, Department of Food Chemistry, Faculty of Agriculture, Tohoku University, Aoba-ku, Sendai 981, Japan 2 The Second Department of Internal Medicine, School of Medicine, Tohoku University, Aoba-ku, Sendai 980, Japan 3 Makino Dermatology Clinic, Aoba-ku, Sendai 981, Japan 4 Division of Internal Medicine, National Sendai Hospital, Miyagino-ku, Sendai 983, Japan (Received January 13, 1992) Summary The developmental mechanism of the bone disorder in- duced by biotin deficiency was studied in osteogenic disorder rats, animals that have a hereditary defect in ascorbic acid-synthesizing ability. The osteogenic disorder rats fed a biotin-deficient diet containing raw egg white were afflicted with bone abnormality including a hunch in the vertebral column. In the case of biotin deficiency, although the ascorbic acid content in the diet was in excess of the required amount, ascorbic acid levels of the plasma and the organs in the rats were significant lower than those of control rats. This suggests that the bone disorder induced by biotin deficiency in the rats may result from the promotion of ascorbic acid consumption or the impairment of ascorbic acid incorporation in the animal tissues. Key Words: osteogenic disorder rat, biotin deficiency, ascorbic acid, bone disorder, acetyl-CoA carboxylase Biotin serves as an essential cofactor for four carboxylases, namely, acetyl- *To whom correspondence should be addressed .
    [Show full text]
  • Georgia's Newborn Screening Panel (Disorders)
    Georgia’s Newborn Screening Panel (Disorders) Organic Acid Fatty Acid Oxidation Amino Acid Hemoglobinopathy Other • Beta Ketothiolase (BKT) • Caritine Uptake • Cobalamin A and B Defect Deficiency (Cbl A,B ) • Long Chain 3 • Glutaric Acidemia type hydroxyl acyl-CoA • Biotinidase I dehydrogenase • Argininosuccinic Deficiency • Congenital • 3OH 3-CH3 Glutaric Acidemia • Sickle Cell • Adrenal Aciduria (HMG) Medium Chain acyl- • Citrullinemia Disease Hyperplasia • Isovaleric Acidemia CoA dehydrogenase • Homocystinuria • Sickle SC Deficiency • Congenital (IVA) • Maple Syrup Urine Disease • Trifunctional Protein Hypothyroidism • 3 Methylcrotonyl-Co A Disease • Sickle Beta Deficiency • Cystic Fibrosis Carboxylase Deficiency • Phenylketonuria Thalassemia • Very Long chain • Galactosemia (3MCC) • Tyrosinemia • Multiple Carboxylase acyl-CoA Deficiency dehydrogenase Deficiency • Methylmalonic Acidemia (MMA) • Propionic Acidemia 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) (3-methel-crow-ton-eel co-A car-box-il-ace de-fish-in-sea) POSITIVE NEWBORN SCREEN What is a positive newborn screen? Newborn screening is done on tiny samples of blood taken from your baby’s heel 24 to 48 hours after birth. Newborn screening tests for rare, hidden disorders that may affect your baby’s health and development. The newborn screen suggests your baby might have a disorder called 3-MCC. There are many other conditions that can cause a similar positive result on newborn screening. A positive newborn screen does not mean your baby has 3-MCC or any of the other conditions above, but it does mean your baby needs more testing to know for sure. Your baby’s doctor will help arrange for more testing by specialists in disorders like 3-MCC. Sometimes, a baby has a positive newborn screen because the mother has a hidden form of 3-MCC.
    [Show full text]
  • Biotin Fact Sheet for Consumers
    Biotin Fact Sheet for Consumers What is biotin and what does it do? Biotin is a B-vitamin found in many foods. Biotin helps turn the carbohydrates, fats, and proteins in the food you eat into the energy you need. How much biotin do I need? The amount of biotin you need each day depends on your age. Average daily recommended amounts are listed below in micrograms (mcg). Life Stage Recommended Amount Birth to 6 months 5 mcg Infants 7–12 months 6 mcg Children 1–3 years 8 mcg Children 4–8 years 12 mcg Biotin is naturally present in some Children 9–13 years 20 mcg foods, such as salmon and eggs. Teens 14–18 years 25 mcg Adults 19+ years 30 mcg Pregnant teens and women 30 mcg Breastfeeding teens and women 35 mcg What foods provide biotin? Many foods contain some biotin. You can get recommended amounts of biotin by eating a variety of foods, including the following: • Meat, fish, eggs, and organ meats (such as liver) • Seeds and nuts • Certain vegetables (such as sweet potatoes, spinach, and broccoli) What kinds of biotin dietary supplements are available? Biotin is found in some multivitamin/multimineral supplements, in B-complex supplements, and in supplements containing only biotin. Am I getting enough biotin? Most people get enough biotin from the foods they eat. However, certain groups of people are more likely than others to have trouble getting enough biotin: • People with a rare genetic disorder called “biotinidase deficiency” • People with alcohol dependence • Pregnant and breastfeeding women 2 • BIOTIN FACT SHEET FOR CONSUMERS What happens if I don’t get enough biotin? Biotin and healthful eating Biotin deficiency is very rare in the United States.
    [Show full text]
  • Biotinidase Deficiency (Biot) Family Fact Sheet
    BIOTINIDASE DEFICIENCY (BIOT) FAMILY FACT SHEET What is a positive newborn screen? What problems can biotinidase deficiency Newborn screening is done on tiny samples of blood cause? taken from your baby’s heel 24 to 36 hours after birth. The blood is tested for rare, hidden disorders that may Biotinidase deficiency is different for each child. Some affect your baby’s health and development. The children have a mild, partial biotinidase deficiency with newborn screen suggests your baby might have a few health problems, while other children may have disorder called biotinidase deficiency. complete biotinidase deficiency with serious complications. A positive newborn screen does not mean your If biotinidase deficiency is not treated, a child might baby has biotinidase deficiency, but it does mean develop: your baby needs more testing to know for sure. • Muscle weakness • Hearing loss You will be notified by your primary care provider or • Vision (eye) problems the newborn screening program to arrange for • Hair loss additional testing. • Skin rashes What is biotinidase deficiency? • Seizures • Developmental delay Biotinidase deficiency affects an enzyme needed to It is very important to follow the doctor’s instructions free biotin (one of the B vitamins) from the food we for testing and treatment. eat, so it can be used for energy and growth. What is the treatment for biotinidase A person with biotinidase deficiency doesn’t have deficiency? enough enzyme to free biotin from foods so it can be used by the body. Biotinidase deficiency can be treated. Treatment is life- long and includes: Biotinidase deficiency is a genetic disorder that is • Daily biotin vitamin pill(s) or liquid.
    [Show full text]