E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy

Abstract

We report the case of a boy who developed a motor neuropathy during infectious episodes at 18mo and 3 y of age. When he was 7 y old, he suffered persistent weakness and areflexia; his resting lactate and pyruvate values were 3.65 mM and 398 µM, respectively (controls: 1.1 ± 0.3 mM and 90 ± 22 µM), and an exercise test demonstrated a lactic acidosis (13.6 mM; controls: 6.4 ± 1.3 mM) with a high pyruvate level (537 µM; controls: 176 ± 15 µM) and a low lactate/pyruvate ratio (24.2;controls: 35 ± 2). The results of polarographic studies on muscle mitochondria suggested a defect in pyruvate oxidation (pyruvate17 ng atom O/min/mg protein; controls: 115 ± 42), whereas glutamate, palmitoylcarnitine, and succinate were good respiratory substrates. The activity of total pyruvate dehydrogenase complex (PDHC) in muscle mitochondria and in fresh mononuclear cells was markedly decreased (9.7 and 0.054 nmol 14CO2/min/mg protein, respectively; controls: 123 ± 4.5 and 0.733 ± 0.03, respectively). Immunochemical analysis in muscle mitochondria demonstrated an absence of the α and β El PDHC subunits. After 2 y of treatment with 500 mg/d thiamine, the patient was clinically improved. A genetic study of the main regions of mutations (exon 10 and 11) in the X chromosome encoding for the El αsubunit of PDHC did not show any mutation. These data indicate that, although genetically different, this case enters in a very rare category of patients with PDHC deficiency without cerebral dysfunction and improved by thiamine + L-carnitine therapy. © 1993 International Pediatric Research Foundation, Inc.