Biotin hyperammonemia

Hyperammonemia occurs in biotin deficiency and the functional deficiency associated with lack of holocarboxylase synthetase (Section 11.2.2.1) and bio-tinidase (Section 11.2.3.1). In deficient rats, the activity of ornithine carbamyl-transferase is two - thirds of that in control animals, as a result of decreased gene expression, although the activities of other urea cycle enzymes are unaffected (Maeda etal., 1996). 

Inborn errors of metabolism may be due to propionyl-CoA carboxylase deficiency, defects in biotin transport or metabolism, methylmalonyl-CoA mutase deficiency, or defects in adenosylcobalamin synthesis. The former two defects result in propionic acidemia, the latter two in methylmalonic acidemia. All cause metabolic acidosis and developmental retardation. Organic acidemias often exhibit hyperammonemia, mimicking ureagenesis disorders, because they inhibit the formation of N-acetylglutamate, an obligatory cofactor for carbamoyl phosphate synthase (Chapter 17). Some of these disorders can be partly corrected by administration of pharmacological doses of the vitamin involved (Chapter 38). Dietary protein restriction is therapeutically useful (since propionate is primarily derived from amino acids). Propionic and methylmalonyl acidemia (and aciduria) results from vitamin B12 deficiency (e.g., pernicious anemia Chapter 38). 

Hyperammonemia is a finding in biotin deficiency. Maeda and colleges have reported that ornithine transcarbamoylase (an enzyme in the urea cycle) is significantly reduced in biotin-deficient rats. 

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