ABSTRACT
Multiple carboxylase deficiency is caused by defective activity of holocarboxylase synthetase. In earlier literature, biotinidase deficiency was referred to as the later infantile form of multiple carboxylase deficiency to distinguish it from the usual neonatal presentation of holocarboxylase synthetase deficiency. Biocytin could compete with biotin as substrate for holocarboxylase synthetase, increasing the concentration of biotin needed for effective holocarboxylase synthesis. The low tissue stores of biotin that result from biotinidase deficiency lead to deficient activity of carboxylases, and this of course results in the lactic acidemia and the accumulation of the other organic acid metabolites. Pyruvate carboxylase may be predominantly affected by biotinidase deficiency in the brain. Neurologic symptomatology could be the result of the toxic effect of local accumulation of lactate and organic acids. A rapid diagnostic method for distinguishing holocarboxylase synthetase abnormality from biotinidase deficiency is the assay of the activity of carboxylases in freshly isolated lymphocytes in the presence and absence of preincubation with biotin.
