DOCSLIB.ORG

MTHFR-Support-Australia-Tech-Book

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
MTHFR-Support-Australia-Tech-Book Patients with MTHFR and methylation issues require a unique approach. The standard products on the market may not be suitable for those with specific issues and therefore a more targeted programme is required. The ability to split your B vitamins is desirable as each patient will have a different need and this allows you to tailor to the individual patient. What is methylation? Methylation or one carbon metabolism is a network of interrelated biochemical pathways for reduction or oxidation and transfer to other compounds. This allows the transfer of a methyl group (one carbon and three hydrogen atoms) onto amino acids, proteins, enzymes and DNA in every cell and tissue of the body. This regulates healing, produces energy, genetic expression of DNA, synthesises neurotransmitters, liver detoxification, immunity and hormonal clearance. So disturbances in this methylation pathway can have significant and widespread effects on many body systems. The key pathways are the folate pathway (of which the MTHFR gene is a crucial final step), the methionine pathway which plays a major role in methyl group metabolism as it allows the recycling of homocysteine back to methionine and elimination via the CBS (Cystathione beta synthase pathway). The methionine synthase enzyme contains a cobalamin cofactor 2 which ensures that with the help of Vitamin B12 the methyl group is transferred to homocysteine. Methionine, which is regenerated from homocysteine is then converted to S-adenosylmethionine (AdoMET). AdoMet then donates the methyl group it obtained from 5- MTHF to over 80 biological methylation reactions, including the methylation of DNA, RNA, proteins, lipids and lipoproteins. The key methyltransferases are the enzyme groups that benefit from this donation of methyl’s by AdoMET. What is MTHFR? MTHFR is a gene, which produces the MTHFR (methylenetetrahydrofolate reductase) enzyme and is considered a key enzyme in one-carbon metabolism, because it catalyses the irreversible conversion of 5,10-methylene THF to 5-methyl tetrahydrofolate.1 5-MTHF is our active folate that is then used in the methylation cycle. Folate Metabolism http://www.aacc.org/publications/cln/2011/january/Pages/FolateMetabolismFigure.aspx What happens if MTHFR activity is reduced? 1. 5-MTHF levels go down 2. Transmethylation cycle slows 3. All tissues except liver and kidney show effects of decreased methylation which leads to: - Decreased neurotransmitter production - Deficiency in glutathione 4. BHMT becomes depleted in choline which causes: homocysteine levels to rise methylation in the liver and kidneys decrease phosphatidylcholine production drops causing cell membrane and myelin instability This may then have affects for the following conditions: Diabetes Chemical sensitivity Cancer Congenital Heart defects Pulmonary embolisms Fibromyalgia Cleft palate Chronic fatigue syndrome Spina Bifida Depression Autism Alcoholism Parkinson’s Disease Addictive behaviours Neural tube defects Insomnia Cardiovascular disease – Downs syndrome atherosclerosis, elevated cholesterol, Autism hypertension, fat metabolism issues Chronic viral infection Immune deficiency Thyroid dysfunction ADD/ADHD Neuropathy MS Recurrent miscarriage Alzheimer’s Infertility Anxiety Schizophrenia Bipolar Allergies References 1. Selhub.J Homocysteine metabolism. Annu.Rev.Nutr. 19,217,1999 2. Weissbach. H and Taylor RT. Roles of Vitamin B12 and folic acid in methionine synthesis. Vitam. Horm. 28, 415, 1970. 3.Robinson K, Mayer EL, et al. Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation. 1995; 92:2825-2830. 4. Homocysteine and Risk of Ischemic Heart Disease and Stroke A Meta-analysis Homocysteine Studies Collaboration. JAMA. 2002;288(16):2015-2022. doi:10.1001/jama.288.16.20 5. Tungtrongchitr R, Pongpaew P, Prayurahong B, et al: Vitamin B12, folic acid and haematological status of 132 Thai vegetarians. Int J Vitam Nutr Res 1993; 63:201-207 Starter B & Methylation Support Specific Indication: Step 1 in methylation support. Initial support for people with the MTHFR gene mutation to aid, assist in or help support as a cofactor for key enzymes in the methylation cycle (Figure 1). Pharmaceutical Effects: Starter B contains six B vitamins without Vitamin B12 or folate. Clinical Benefits: The B vitamins all act as cofactors in the methylation cycle to support critical enzymes integral to the pathway. Thiamin (B1) and Pyridoxine (B6) are confirmed by human clinical trials to work together to cause a decrease in DNA glycation. 1-3Human studies show that the effect of Thiamin decreasing DNA glycation results in higher levels of methylation.2,3 Riboflavin (B2) acts as a cofactor for folate and so increases methylation. It is the limiting nutrient for pyridoxine folate and B12 metabolism.2,3,4 It can also assist niacin in reducing excessive DNA methylation.2 It is the cofactor for the MTHFR gene. Niacin (nicotinamide, B3) and its derivative nicotinamide are dietary precursors of nicotinamide adenine dinucleotide (NAD). NAD functions in oxidation-reduction (redox) reactions and non-redox reactions. 11 NAD is an important cofactor for MTRR (methionine synthase reductase) enzyme. http://lpi.oregonstate.edu/mic/vitamins/vitamin-B6 Figure 1. B vitamins & step 1 in methylation support & one-carbon metabolism. Pantothenic acid (B5) is confirmed by human clinical trials to improve the nutritional and metabolic status of the genome including DNA methylation,16,17 particularly for mental health in adults and psychology in children. 18,19,20 Pyridoxine (B6) is confirmed by human clinical trials to increase DNA methylation levels and work together with riboflavin, folate, and B12. 21,22Deficiency of Pyridoxine in animals results in reduction of DNA methylation. 23,24 B6 is an important cofactor for the CBS pathway. Biotin (B7) is confirmed by human clinical trials to be related to folate in its DNA methylation functions16,25. It works with other vitamins, such as pantothenic acid, riboflavin, niacin, pyridoxine, folate and B12, to play essential roles in maintaining mitochondrial functions including DNA methylation.2 All doses are safe according to the Australian RDI and the U. S. DRI. References 1Polizzi FC, Andican G, Çetin E, Civelek S, Yumuk V, Burçak G. Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy. Experimental and clinical endocrinology & diabetes, June 2012, 120(6), 329-34. PubMed PMID: 22231921 2 Schupp N, Dette EM, Schmid U, Bahner U, Winkler M, Heidland A, Stopper H. Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients. Naunyn-Schmiedeberg's archives of pharmacology, September 2008, 378(3), 283-91. PubMed PMID: 18509620 3 Schupp N, Schmid U, Heidland A, Stopper H. New approaches for the treatment of genomic damage in end-stage renal disease. Journal of renal nutrition, January 2008, 18(1), 127-33. PubMed PMID: 18089459 4 Maslinska D, Laure-Kamionowska M, Maslinski S. Methyl-CpG binding protein 2, receptors of innate immunity and receptor for advanced glycation end-products in human viral meningoencephalitis. Folia neuropathologica, 2014, 52(4), 428-35. PubMed PMID: 25574748 5 Lu W, Li J, Ren M, Zeng Y, Zhu P, Lin L, Lin D, Hao S, Gao Q, Liang J, Yan L, Yang C. Role of the mevalonate pathway in specific CpG site demethylation on AGEs-induced MMP9 expression and activation in keratinocytes. Molecular and cellular endocrinology, August 2015, 15(411), 121-129. PubMed PMID: 25916956 6 Powers HJ, Hill MH, Welfare M, Spiers A, Bal W, Russell J, Duckworth Y, Gibney E, Williams EA, Mathers JC. Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study). Cancer epidemiology, biomarkers & prevention, October 2007, 16(10), 2128-35. PubMed PMID: 17932361 7 Figueiredo JC, Levine AJ, Grau MV, Midttun O, Ueland PM, Ahnen DJ, Barry EL, Tsang S, Munroe D, Ali I, Haile RW, Sandler RS, Baron JA. Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation. Cancer epidemiology, biomarkers & prevention, August 2008, 17(8), 2136-45. PubMed PMID: 18708408 8Nedrebø BG, Hustad S, Schneede J, Ueland PM, Vollset SE, Holm PI, Aanderud S, Lien EA. Homocysteine and its relation to B-vitamins in Graves' disease before and after treatment: effect modification by smoking. Journal of internal medicine, November 2003, 254(5), 504-12. PubMed PMID: 14535973 9Madigan SM, Tracey F, McNulty H, Eaton-Evans J, Coulter J, McCartney H, Strain JJ. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people. American journal of clinical nutrition, August 1998, 68(2), 389-95. PubMed PMID: 9701198 10Premkumar VG, Yuvaraj S, Shanthi P, Sachdanandam P. Co-enzyme Q10, riboflavin and niacin supplementation on alteration of DNA repair enzyme and DNA methylation in breast cancer patients undergoing tamoxifen therapy. British journal of nutrition, December 2008, 100(6), 1179-82. PubMed PMID: 18377693 11Penberthy WT, Kirkland JB. Niacin. In:Erdman JW, MacDonald I, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames: International Life Sciences Institute;2012:293-306 12Sun WP, Li D, Lun YZ, et al. Excess nicotinamide inhibits methylation-mediated degradation of catecholamines in normotensives and hypertensives. Hypertension
Load more

Recommended publications
  • 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]
  • Abstracts from the 9Th Biennial Scientific Meeting of The
    International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):15 DOI 10.1186/s13633-017-0054-x MEETING ABSTRACTS Open Access Abstracts from the 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society (APPES) and the 50th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE) Tokyo, Japan. 17-20 November 2016 Published: 28 Dec 2017 PS1 Heritable forms of primary bone fragility in children typically lead to Fat fate and disease - from science to global policy a clinical diagnosis of either osteogenesis imperfecta (OI) or juvenile Peter Gluckman osteoporosis (JO). OI is usually caused by dominant mutations affect- Office of Chief Science Advsor to the Prime Minister ing one of the two genes that code for two collagen type I, but a re- International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):PS1 cessive form of OI is present in 5-10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that Attempts to deal with the obesity epidemic based solely on adult be- play a role in the processing of collagen type I protein (BMP1, havioural change have been rather disappointing. Indeed the evidence CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, PLOD2, SERPINF1, that biological, developmental and contextual factors are operating SERPINH1, SEC24D, SPARC, from the earliest stages in development and indeed across generations TMEM38B), or interfere with osteoblast function (SP7, WNT1). Specific is compelling. The marked individual differences in the sensitivity to the phenotypes are caused by mutations in SERPINF1 (recessive OI type obesogenic environment need to be understood at both the individual VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter and population level.
    [Show full text]
  • Anti-MMAB Antibody (ARG55862)
    Product datasheet [email protected] ARG55862 Package: 100 μl anti-MMAB antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes MMAB Tested Reactivity Hu Predict Reactivity Ms Tested Application WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name MMAB Antigen Species Human Immunogen KLH-conjugated synthetic peptide corresponding to aa. 50-81 (Center) of Human MMAB. Conjugation Un-conjugated Alternate Names ATR; cob; cblB; CFAP23; Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial; EC 2.5.1.17; Cob(I)alamin adenosyltransferase; Methylmalonic aciduria type B protein Application Instructions Application table Application Dilution WB 1:1000 Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control HepG2 Calculated Mw 27 kDa Properties Form Liquid Purification Purification with Protein A and immunogen peptide. Buffer PBS and 0.09% (W/V) Sodium azide Preservative 0.09% (W/V) Sodium azide Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C or below. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. Note For laboratory research only, not for drug, diagnostic or other use. www.arigobio.com 1/2 Bioinformation Database links GeneID: 326625 Human Swiss-port # Q96EY8 Human Gene Symbol MMAB Gene Full Name methylmalonic aciduria (cobalamin deficiency) cblB type Background This gene encodes a protein that catalyzes the final step in the conversion of vitamin B(12) into adenosylcobalamin (AdoCbl), a vitamin B12-containing coenzyme for methylmalonyl-CoA mutase.
    [Show full text]
  • Oral Presentations
    Journal of Inherited Metabolic Disease (2018) 41 (Suppl 1):S37–S219 https://doi.org/10.1007/s10545-018-0233-9 ABSTRACTS Oral Presentations PARALLEL SESSION 1A: Clycosylation and cardohydrate disorders O-002 Link between glycemia and hyperlipidemia in Glycogen Storage O-001 Disease type Ia Hoogerland J A1, Hijmans B S1, Peeks F1, Kooijman S3, 4, Bos T2, Fertility in classical galactosaemia, N-glycan, hormonal and inflam- Bleeker A1, Van Dijk T H2, Wolters H1, Havinga R1,PronkACM3, 4, matory gene expression interactions Rensen P C N3, 4,MithieuxG5, 6, Rajas F5, 6, Kuipers F1, 2,DerksTGJ1, Reijngoud D1,OosterveerMH1 Colhoun H O1,Rubio-GozalboME2,BoschAM3, Knerr I4,DawsonC5, Brady J J6,GalliganM8,StepienKM9, O'Flaherty R O7,MossC10, 1Dep Pediatrics, CLDM, Univ of Groningen, Groningen, Barker P11, Fitzgibbon M C6, Doran P8,TreacyEP1, 4, 9 Netherlands, 2Lab Med, CLDM, Univ of Groningen, Groningen, Netherlands, 3Dep of Med, Div of Endocrinology, LUMC, Leiden, 1Dept Paediatrics, Trinity College Dublin, Dublin, Ireland, 2Dept Paeds and Netherlands, 4Einthoven Lab Exp Vasc Med, LUMC, Leiden, Clin Genetics, UMC, Maastricht, Netherlands, 3Dept Paediatrics, AMC, Netherlands, 5Institut Nat Sante et Recherche Med, Lyon, Amsterdam, Netherlands, 4NCIMD, TSCUH, Dublin, Ireland, 5Dept France, 6Univ Lyon 1, Villeurbanne, France Endocrinology, NHS Foundation Trust, Birmingham, United Kingdom, 6Dept Clin Biochem, MMUH, Dublin, Ireland, 7NIBRT Glycoscience, Background: Glycogen Storage Disease type Ia (GSD Ia) is an NIBRT, Dublin, Ireland, 8UCDCRC,UCD,Dublin,Ireland,9NCIMD, inborn error of glucose metabolism characterized by fasting hypo- MMUH, Dublin, Ireland, 10Conway Institute, UCD, Dublin, Ireland, glycemia, hyperlipidemia and fatty liver disease. We have previ- 11CBAL, NHS Foundation, Cambridge, United Kingdom ously reported considerable heterogeneity in circulating triglycer- ide levels between individual GSD Ia patients, a phenomenon that Background: Classical Galactosaemia (CG) is caused by deficiency of is poorly understood.
    [Show full text]
  • Case Report Methylmalonic Acidemia with Novel MUT Gene Mutations
    Case Report Methylmalonic Acidemia with Novel MUT Gene Mutations Commented [A 1]: Important: 1.As per the journal, units of measurement should be Inusha Panigrahi, Savita Bhunwal, Harish Varma, and Simranjeet Singh presented simply and concisely using System International (SI) units; please ensure that units are Department of Pediatrics, Advanced Pediatric Centre, PGIMER, Chandigarh, India presented using the SI system at all instances. 2.References for some previously published data is Correspondence: Inusha Panigrahi; [email protected] missing. Please ensure that references are provided Methylmalonic acidemia (MMA) is a rare inherited metabolic disorder caused by deficiency wherever required. of the enzyme methylmalonyl-CoA mutase. The disease is presented in early infancy by 3.Informed consent from the patient is required and lethargy, vomiting, failure to thrive, encephalopathy and is deadly if left untreated. A 5-years should be mentioned in the manuscript. old boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of For more information, please refer to the guidelines at 11 months, and poor weight gain. He was admitted and evaluated for metabolic causes and https://www.hindawi.com/journals/crig/guidelines/. diagnosed as methylmalonic acidemia (MMA). He was treated with vit B12 and carnitine Commented [A 2]: As per the journal’s guidelines, supplements and has been on follow-up for the last 3 years. Mutation analysis by next please provide email addresses of all the authors. generation sequencing (NGS), supplemented with Sanger sequencing, revealed two novel Formatted: Right: 0 cm, Space Before: 0 pt, Line variants in the MUT gene responsible for MMA in exon 5 and exon 3.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Mut , Mut , Cbla, Cblb
    0031-3998/07/6202-0225 PEDIATRIC RESEARCH Vol. 62, No. 2, 2007 Copyright © 2007 International Pediatric Research Foundation, Inc. Printed in U.S.A. Long-Term Outcome in Methylmalonic Acidurias Is Influenced (by the Underlying Defect (mut0, mut؊, cblA, cblB FRIEDERIKE HO¨ RSTER, MATTHIAS R. BAUMGARTNER, CAROLINE VIARDOT, TERTTU SUORMALA, PETER BURGARD, BRIAN FOWLER, GEORG F. HOFFMANN, SVEN F. GARBADE, STEFAN KO¨ LKER, AND E. REGULA BAUMGARTNER Department of General Pediatrics [F.H., P.B., G.F.H., S.F.G., S.K.], Division of Inborn Metabolic Diseases, University Children’s Hospital, D-69120 Heidelberg, Germany; Metabolic Unit [C.V., T.S., B.F. E.R.B.], University Children’s Hospital Basel, CH-4005 Basel, Switzerland; Division of Metabolism and Molecular Pediatrics [M.R.B.], University Children’s Hospital Zu¨rich, CH-8032 Zu¨rich, Switzerland ABSTRACT: Isolated methylmalonic acidurias comprise a hetero- mut0 defect with complete loss of MCM activity (1). Both geneous group of inborn errors of metabolism caused by defects of defects are caused by mutations in the MUT gene and there- 0 – methylmalonyl-CoA mutase (MCM) (mut , mut ) or deficient syn- fore belong to the same complementation group (MIM thesis of its cofactor 5=-deoxyadenosylcobalamin (AdoCbl) (cblA, #251000). Using somatic complementation analysis, defects cblB). The aim of this study was to compare the long-term outcome of AdoCbl synthesis can be subdivided into several groups, in patients from these four enzymatic subgroups. Eighty-three pa- tients with isolated methylmalonic acidurias (age 7–33 y) born three of which cause isolated methylmalonic acidurias, i.e. between 1971 and 1997 were enzymatically characterized and pro- cblA, cblB, and, less frequently, cblD defects (2).
    [Show full text]
  • Natalis Information Sheet V03
    Sema4 Natalis Clinical significance of panel Sema4 has designed and validated Natalis, a supplemental newborn screening panel offered for newborns, infants, and young children. This test may be offered to parents as an addition to the state mandated newborn screening that their child received at birth. This panel includes next-generation sequencing, targeting genotyping, and multiplex ligation-dependent probe amplification in a total of 166 genes to screen for 193 conditions that have onset in infancy or early childhood and for which there is treatment or medical management that, when administered early in an infant or child’s life, will significantly improve the clinical outcome. Conditions included in this panel were curated based on criteria such as: inclusion on current state mandated newborn screening panels, onset of symptoms occurring <10 years of age, evidence of high penetrance (>80%), and availability of a treatment or improvement in life due to early intervention. Sema4 has also designed and validated a pediatric pharmacogenetic (PGx) genotyping panel as an adjunct test to the Natalis assay. This panel includes 10 genes and 41 sequence variants involved in drug response variability. The genes and variants in the PGx genotyping panel inform on more than 40 medications that can be prescribed during childhood. Currently, there is evidence supporting the clinical utility of testing for certain PGx variants for which there are genotype-directed clinical practice recommendations for selected gene/drug pairs. Approximately 95% of all individuals will carry at least one clinically actionable variant in the PGx panel. Testing methods, sensitivity, and limitations A cheek swab, saliva sample, or blood sample is provided by the child and a biological parent.
    [Show full text]
  • Downloaded from the App Store and Nucleobase, Nucleotide and Nucleic Acid Metabolism 7 Google Play
    Hoytema van Konijnenburg et al. Orphanet J Rare Dis (2021) 16:170 https://doi.org/10.1186/s13023-021-01727-2 REVIEW Open Access Treatable inherited metabolic disorders causing intellectual disability: 2021 review and digital app Eva M. M. Hoytema van Konijnenburg1†, Saskia B. Wortmann2,3,4†, Marina J. Koelewijn2, Laura A. Tseng1,4, Roderick Houben6, Sylvia Stöckler‑Ipsiroglu5, Carlos R. Ferreira7 and Clara D. M. van Karnebeek1,2,4,8* Abstract Background: The Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disabil‑ ity (collectively ‘treatable IDs’). Our aim is to update the 2012 review on treatable IDs and App to capture the advances made in the identifcation of new IMDs along with increased pathophysiological insights catalyzing therapeutic development and implementation. Methods: Two independent reviewers queried PubMed, OMIM and Orphanet databases to reassess all previously included disorders and therapies and to identify all reports on Treatable IDs published between 2012 and 2021. These were included if listed in the International Classifcation of IMDs (ICIMD) and presenting with ID as a major feature, and if published evidence for a therapeutic intervention improving ID primary and/or secondary outcomes is avail‑ able. Data on clinical symptoms, diagnostic testing, treatment strategies, efects on outcomes, and evidence levels were extracted and evaluated by the reviewers and external experts. The generated knowledge was translated into a diagnostic algorithm and updated version of the App with novel features. Results: Our review identifed 116 treatable IDs (139 genes), of which 44 newly identifed, belonging to 17 ICIMD categories.
    [Show full text]
  • CENTOGENE's Severe and Early Onset Disorder Gene List
    CENTOGENE’s severe and early onset disorder gene list USED IN PRENATAL WES ANALYSIS AND IDENTIFICATION OF “PATHOGENIC” AND “LIKELY PATHOGENIC” CENTOMD® VARIANTS IN NGS PRODUCTS The following gene list shows all genes assessed in prenatal WES tests or analysed for P/LP CentoMD® variants in NGS products after April 1st, 2020. For searching a single gene coverage, just use the search on www.centoportal.com AAAS, AARS1, AARS2, ABAT, ABCA12, ABCA3, ABCB11, ABCB4, ABCB7, ABCC6, ABCC8, ABCC9, ABCD1, ABCD4, ABHD12, ABHD5, ACACA, ACAD9, ACADM, ACADS, ACADVL, ACAN, ACAT1, ACE, ACO2, ACOX1, ACP5, ACSL4, ACTA1, ACTA2, ACTB, ACTG1, ACTL6B, ACTN2, ACVR2B, ACVRL1, ACY1, ADA, ADAM17, ADAMTS2, ADAMTSL2, ADAR, ADARB1, ADAT3, ADCY5, ADGRG1, ADGRG6, ADGRV1, ADK, ADNP, ADPRHL2, ADSL, AFF2, AFG3L2, AGA, AGK, AGL, AGPAT2, AGPS, AGRN, AGT, AGTPBP1, AGTR1, AGXT, AHCY, AHDC1, AHI1, AIFM1, AIMP1, AIPL1, AIRE, AK2, AKR1D1, AKT1, AKT2, AKT3, ALAD, ALDH18A1, ALDH1A3, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDOA, ALDOB, ALG1, ALG11, ALG12, ALG13, ALG14, ALG2, ALG3, ALG6, ALG8, ALG9, ALMS1, ALOX12B, ALPL, ALS2, ALX3, ALX4, AMACR, AMER1, AMN, AMPD1, AMPD2, AMT, ANK2, ANK3, ANKH, ANKRD11, ANKS6, ANO10, ANO5, ANOS1, ANTXR1, ANTXR2, AP1B1, AP1S1, AP1S2, AP3B1, AP3B2, AP4B1, AP4E1, AP4M1, AP4S1, APC2, APTX, AR, ARCN1, ARFGEF2, ARG1, ARHGAP31, ARHGDIA, ARHGEF9, ARID1A, ARID1B, ARID2, ARL13B, ARL3, ARL6, ARL6IP1, ARMC4, ARMC9, ARSA, ARSB, ARSL, ARV1, ARX, ASAH1, ASCC1, ASH1L, ASL, ASNS, ASPA, ASPH, ASPM, ASS1, ASXL1, ASXL2, ASXL3, ATAD3A, ATCAY, ATIC, ATL1, ATM, ATOH7,
    [Show full text]
  • The Genotype Analysis and Prenatal Genetic Diagnosis Among 244 Pedigrees with Methylmalonic Aciduria in China
    The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China Shuang Hu First Aliated Hospital of Zhengzhou University Lina Liu First Aliated Hospital of Zhengzhou University Zhihui Jiao First Aliated Hospital of Zhengzhou University Xiangdong Kong ( [email protected] ) First Aliated Hospital of Zhengzhou University Research Article Keywords: methylmalonic aciduria, MMACHC, MUT, variant, prenatal genetic diagnosis Posted Date: February 24th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-249909/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/20 Abstract To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees. Gene analyses were performed for 244 pedigrees. There are 130 families, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis. Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methymalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without hyperhomocysteinemia. MMACHC, MUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 foetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants.
    [Show full text]
  • Diseases Catalogue
    Diseases catalogue AA Disorders of amino acid metabolism OMIM Group of disorders affecting genes that codify proteins involved in the catabolism of amino acids or in the functional maintenance of the different coenzymes. AA Alkaptonuria: homogentisate dioxygenase deficiency 203500 AA Phenylketonuria: phenylalanine hydroxylase (PAH) 261600 AA Defects of tetrahydrobiopterine (BH 4) metabolism: AA 6-Piruvoyl-tetrahydropterin synthase deficiency (PTS) 261640 AA Dihydropteridine reductase deficiency (DHPR) 261630 AA Pterin-carbinolamine dehydratase 126090 AA GTP cyclohydrolase I deficiency (GCH1) (autosomal recessive) 233910 AA GTP cyclohydrolase I deficiency (GCH1) (autosomal dominant): Segawa syndrome 600225 AA Sepiapterin reductase deficiency (SPR) 182125 AA Defects of sulfur amino acid metabolism: AA N(5,10)-methylene-tetrahydrofolate reductase deficiency (MTHFR) 236250 AA Homocystinuria due to cystathionine beta-synthase deficiency (CBS) 236200 AA Methionine adenosyltransferase deficiency 250850 AA Methionine synthase deficiency (MTR, cblG) 250940 AA Methionine synthase reductase deficiency; (MTRR, CblE) 236270 AA Sulfite oxidase deficiency 272300 AA Molybdenum cofactor deficiency: combined deficiency of sulfite oxidase and xanthine oxidase 252150 AA S-adenosylhomocysteine hydrolase deficiency 180960 AA Cystathioninuria 219500 AA Hyperhomocysteinemia 603174 AA Defects of gamma-glutathione cycle: glutathione synthetase deficiency (5-oxo-prolinuria) 266130 AA Defects of histidine metabolism: Histidinemia 235800 AA Defects of lysine and
    [Show full text]