A 2-week-old boy had profound generalized weakness, hypotonia, hyporeflexia, macroglossia, and severe lactic acidosis. The infant improved spontaneously: he held his head at 4 1/2 months, rolled over at 7 months, and walked by 16 months. At 33 months of age, he had mild proximal weakness. Macroglossia disappeared by age 4 months. Blood lactic acid declined steadily and was normal by 14 months of age. Histochemical and ultrastructural studies of muscle biopsy specimens obtained at 1 and 7 months of age showed excessive mitochondria, lipid, and glycogen; a third biopsy at age 36 months showed only atrophy of scattered fibers. Cytochrome c oxidase stain was positive in fewer than 5% of fibers in the first biopsy, in approximately 60% of fibers in the second biopsy, and in all fibers in the third biopsy. Biochemical analysis showed an isolated defect of cytochrome c oxidase activity, which was only 8% of the lowest control level in the first biopsy; the activity increased to 47% in the second biopsy and was higher than normal in the third. In contrast to that in the fatal infantile form of cytochrome c oxidase deficiency, the enzyme defect in this condition is reversible. The biochemical basis for this difference remains to be explained.

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Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.