Carboxylase defect, multiple D81.8

Autosomal recessive inherited disease (mutations of the HLCS gene; gene locus: 21q22.1). Pathogenetically, a deficiency in the enzyme activity of pyruvate, propionyl-CoA and 3-methylcrotonyl-CoA carboxylase causes disturbances in the breakdown of carbohydrates and the amino acids leucine, isoleucine, valine, threonine and methionine.

Severe, episodically occurring exanthema (erythematous, eczematous, possibly weeping); alopecia possible, acidosis (organoaciduria, vomiting, dehydration, tachypnea). Tendency to leukopenia or monocytopenia, disturbance of T-lymphocyte function. In severe cases, ataxia, convulsions and CT changes of the brain similar to leukodystrophy still occur.

1. Narang MA et al (2004) Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. Hum Mol Genet 13: 15-23
2. Sweetman L, Nyhan WL (1986) Inheritable biotin-treatable disorders and associated phenomena. Ann Rev Nutr 6: 317-343
3. Thoene J, Baker H, Yoshino M, Sweetman L (1979) Biotin-responsive carboxylase deficiency with subnormal plasma and urinary biotin. New Engl J Med 304: 817-820