Reassessment of biotin-responsiveness in “unresponsive” propionyl CoA carboxylase deficiency

Abstract

HIGH-DOSAGE BIOTIN TREATMENT of multiple carboxylase deficiency markedly improves the clinical manifestations of the disorder and increases the activities of the three biotin-dependent enzymes, propionyl CoA carboxylase, fi-methylcrotonyl CoA carboxylase, and pyruvate carboxylase, 12 to near-normal or normal values. In contrast, biotin supplementation in isolated PCC deficiency fails to restore the residual enzyme activity even to near-normal in either peripheral blood leukocytes or cultured fibroblasts from affected individuals?. ~ Consequently, biotin treatment has been assumed to provide no therapeutic benefits to these unresponsive patients and has usually been discontinued. Our re-examination of the effect of biotin on PCC activity in peripheral blood leukocytes and in cultured fibroblasts from patients with isolated PCC-deficiency, presented here, has revealed that biotin does increase residual activities 122% in leukocytes and 76% in cultured fibroblasts. Although even the enhanced activities remain considerably below the normal range, some approach 15 to 20% of normal. If similar increases are also achieved in