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A novel metabolic disorder in the degradation pathway of endogenous methanol due to a mutation in the gene of alcohol dehydrogenase

Razzaghy Azar, M ; Sharif University of Technology | 2021

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  1. Type of Document: Article
  2. DOI: 10.1016/j.clinbiochem.2021.01.007
  3. Publisher: Elsevier Inc , 2021
  4. Abstract:
  5. Background: A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. Results: This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1–4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and appeared healthy. Organ evaluations and his laboratory tests were normal. Toxicological evaluation of his blood showed a high methanol level [12.2 mg/dL (3.8 mmol/L), normal range up to 3.5 mg/dL (1.09 mmol/L) while the formaldehyde level was undetectable. The finding of liver function tests that were within normal limits, coupled with a normal eye examination and size of the liver, elevated blood methanol levels and an undetectable formaldehyde level, suggested ADH insufficiency. Adding zinc to the drug regimen 15 mg/daily dramatically reduced the patient's methanol level and alleviated the abnormal symptoms. When zinc supplementation was discontinued, the patient relapsed into a coma and hemodialysis was once again required. A homozygous mutation in ADH1C gene located at exon 3 was found, and both parents were heterozygous for this mutation. Conclusion: Accumulation of methanol due to mutation in ADH1C gene may result in drunkenness and ataxia, and leads to coma. This condition can be successfully treated with zinc supplementation as the cofactor of ADH. © 2021
  6. Keywords:
  7. Alcohol dehydrogenase 1c ; Diazoxide ; Formaldehyde ; Meglitinide ; Methanol dehydrogenase ; Repaglinide ; Starch ; Unclassified drug ; Zinc ; Alcohol blood level ; Balance disorder ; Body weight loss ; Case report ; Clinical article ; Colorimetry ; Comatose patient ; Consciousness ; Dysarthria ; Enzyme degradation ; Euphoria ; Evaluation study ; Exon ; Family history ; Follow up ; Gene mutation ; Genetic analysis ; Genetic code ; Genetic toxicology ; Hemodialysis patient ; Hospital admission ; Human ; Hypoglycemia ; Laboratory test ; Length of stay ; Non insulin dependent diabetes mellitus ; Nuclear magnetic resonance imaging ; Polydipsia ; Polyuria ; Priority journal ; School child ; Somnolence ; vertigo ; Alcohol intoxication ; Blood ; Complication ; Genetics ; Hemodialysis ; Inborn error of metabolism ; Metabolic disorder ; Metabolism ; Procedures ; Alcohol Dehydrogenase ; Alcoholic Intoxication ; Ataxia ; Child ; Coma ; Exons ; Heterozygote ; Humans ; Liver ; Male ; Metabolic Diseases ; Metabolism, Inborn Errors ; Methanol ; Mutation ; Renal Dialysis ; Treatment Outcome
  8. Source: Clinical Biochemistry ; Volume 90 , 2021 , Pages 66-72 ; 00099120 (ISSN)
  9. URL: https://www.sciencedirect.com/science/article/pii/S0009912021000230?via%3Dihub