CLINICAL AND MOLECULAR HETEROGENEITY OF CYTOCHROME-C-OXIDASE DEFICIENCY IN THE NEWBORN

We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenat al cerebral malformations, neurological distress with ketoacidosis, se vere myopathy, or isolated respiratory control failure. Lactic acid wa s elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochrome c oxidase deficiency. Among the pa tients, the enzymatic defect differed in the level of residual activit y, expression in different tissues and subunit composition in muscle ( as analysed by immunohistochemistry). Southern blot analysis of the mi tochondrial DNA was normal in 7 patients. The heterogeneity of cytochr ome c oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutatio ns.