PARTIAL 3-METHYLCROTONYL-COA CARBOXYLASE DEFICIENCY IN AN INFANT WITHFATAL OUTCOME DUE TO PROGRESSIVE RESPIRATORY-FAILURE

Isolated partial 3-methylcrotonyl-CoA carboxylase (MCC) deficiency has been described to be the cause for a distinct relatively mild clinica l picture in a single patient. We describe another patient with isolat ed partial MCC deficiency who suffered from failure to thrive, muscula r hypotonia and progressive respiratory insufficiency with fatal outco me at the age of 6.5 months. MCC deficiency was suspected at 3 months of age on the basis of mildly elevated urinary excretion of 3-hydroxyi sovaleric acid and 3-methylcrotonylglycine and confirmed by enzyme ana lysis in lymphocyte and fibroblast homogenates. Residual MCC activity in lymphocytes was 25% of the mean normal value. Residual activity in fibroblasts was lower than in lymphocytes (3.8% of mean normal) and no t significantly different from that in patients with complete MCC defi ciency. However, the residual incorporation of C-14-isovalerate into m acromolecules in intact fibroblasts, was clearly higher (28% of mean n ormal) than in fibroblasts with complete MCC deficiency (<4%). In both patients with partial deficiency the residual MCC activity was higher in lymphocytes than in fibroblasts. Clinical symptoms and signs in ou r patient attributable to MCC deficiency include muscular hypotonia, f ailure to thrive (already present at birth), progressive respiratory f ailure due to diaphragmatic paresis and a moderate brain atrophy. The clinical presentation was more severe than in many patients with compl ete MCC deficiency. Dietary therapy was biochemically effective as sho wn by normalization of organic acid excretion, however, had no effect on the CNS symptoms. Conclusion We speculate that the severity of the disease could be related primarily to deficiency of MCC activity in th e brain. Variable MCC activity among various organs may explain the pe culiar clinical picture in this patient.