Mitochondrial myopathy and familial thiamine deficiency

We studied two siblings with a mitochondrial myopathy, familial thiamine de ficiency, and an A3243G mutation of the mitochondrial DNA (mtDNA). The elde r brother (patient 1, now 36 years old) developed myopathy and beriberi hea rt at 20 years of age. Thiamine therapy resolved the cardiac symptoms and h yperpyruvicemia and improved the myopathy. The younger brother presented ag ed 19 years with a myopathy (patient 2, now 35 years old). Thiamine deficie ncy was present in the siblings and parents, and ragged-red fibers (RRFs) w ere noted in muscle biopsies from the siblings, Analysis 17 years later dem onstrated thiamine malabsorption and an A3243G mutation of the mtDNA in bot h siblings and their mother, progressive myopathy, and an increased number of RRFs and elevated serum CKMB activity in patient 1. Thiamine treatment d ecreased the serum concentrations of lactate and pyruvate in patient 2, but not patient 1. The role of thiamine in mitochondrial dysfunction caused by an electron transfer disorder in the setting of A3243G mtDNA mutation is d iscussed. (C) 2000 John Wiley & Sons, Inc.