Six infants with thiamine-responsive congenital lactic acidosis (CLA), normal pyruvate dehydrogenase complex activity, and no evidence of mitochondrial encephalomyopathy, are reported from Tottori University, Yonago; National Children’s Medical Center, Tokyo, and other centers in Japan. Histochemical investigation of muscle from 3 patients showed no ragged red fibers and normal cytochrome C oxidase activity. Two patients were typical of Leigh syndrome, with symmetrical basal ganglia lesions on neuroimaging. Three patients were siblings born to consanguineous parents, with similar clinical manifestations of cardiomyopathy in infancy. One patient was diagnosed in the neonatal period, and high-dose thiamine therapy (17-35 mg/kg day) was begun before the occurrence of acute neurologic deficit; at age 2, the brain MRI was normal and at age 4, her development was normal. Although rare, thiamine-responsive CLA should be recognized early by prompt measurement of lactate and pyruvate levels. The monitoring of lactate and pyruvate is helpful in determining the most effective dose of thiamine. [1]
COMMENT. Congenital lactic acidosis (CLA) usually leads to metabolic decompensation or neurologic deterioration, such as Leigh syndrome or mitochondrial encephalopathy. In rare cases, early diagnosis and treatment with large doses of thiamine may result in amelioration of symptoms, normal lactate and pyruvate levels, and normal development.