Deficiency of holocarboxylase synthetase (the enzyme that attaches biotin to the apo enzymes) results in a disorder in which propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase, pyruvate carboxylase and acetyl-CoA carboxylase are all deficient. Patients with the disorder have clinical symptoms and biochemical abnormalities associated with deficiencies of the individual enzymes. Most present in the neonatal period with vomiting, ketoaciduria, lactic acidosis, convulsions and hypotonia, leading to coma and death if untreated. Some patients present later and have alopecia and an erythematomous rash. Multiple carboxylase deficiency also results from deficiency of biotinidase, an enzyme involved in the recycling of biotin. Patients with this disorder have a variable phenotype with onset from a few weeks of age up to 10 years. Symptoms include seizures, hypotonia, developmental delay, ataxia, alopecia and erythematomous rash. Both types of multiple carboxylase deficiency respond dramatically to treatment with oral bioin and prognosis is good if the condition is diagnosed and treated early.
ENZYME TEST: Propionyl-Co A carboxylase, 3-methylcrotonyl-CoA carboxylase and pyruvate carboxylase are assayed in cells grown in low-biotin medium for indirect diagnosis of holocarboxylase synthetase deficiency. Assay of biotinidase in plasma is available in the Paediatrics Department laboratory at Guy’s Hospital for diagnosis of biotinidase deficiency.