Sensitivity to Carbohydrate in a Patient with Familial Intermittent Lactic Acidosis and Pyruvate Dehydrogenase Deficiency

Abstract

Pediat. Res. 10: 7 13-720 (1976) Alaninuria metabolic acidosis inborn e r r o r of metabolism pyruvate dehydrogenase deficiency lactic acidosis skin fibrosis m e n t a l retardation Extract diet containing 65% carbohydrates precipitated a severe episode of lactic acidosis and whose two sisters died of the same disorder. His A 9-year-old boy with severe mental and growth retardation and cultured skin fibroblasts proved to be deficient i n PDH activity, diffuse neurologic damage had minimal elevation of blood pyruvate (0.21 mM) and lactate (2.1 mM) on a normal diet hut developed CASE REPORTS life-threatening lactic acidosis (pH 7.14; lactate 21.0 mM) on a diet containing 65% carbohydrates and 15% fat. Subsequently, CASE I blood pyruvate levels rose significantly higher than in 16 control subjects during a glucose tolerance test whereas the glucose levelsThe propositus. JB. was born without complications at term were normal. after a normal pregnancy. Birth weight. length, and head circumTwo sisters died with spontaneous lactic acidosis and an otherwise ference were normal. He was hypoactive and hypotonic and was similar clinical course. ~h~i~ brains at autopsy were severely said to have a "peculiar" odor. Psychomotor development virtualdeficient in myelin but showed no evidence for active &myelination.ly ceased by 3 months of age; growth decelerated at 2 years and Cultured skin fibroblasts from the patient oxidized respiratory infections despite 4 years in a state hospital. Severe normally. ~h~ activity of the pyruvate dehydrogenase complex in neurologic deficits were noted early and were similar to those cell-free extracts (59* 16 pmol/min/mg protein) was significantly described below. less than that for control subjects (389* 35; P < 0.001), but the When seen at age 8.5 years, the patient was severely stunted in activities pyruvate decarboxylase and of the 2-oxoglutarate de-growth, profoundly retarded. had flexion deformities of the hands hydrogenase complex were within the normal range. Pyruvate de-and feet, but had no dysplastic features. Weight was 11.4 kg; hydrogenase levels in extracts of the parents9 cells were midway height, 95 cm; and head circumference. 50 cm. His pulse rate was between those of the patients and the control subjects. ~i~i~~ never found to be below 100. He appeared to hear and see and had experiments, addition of excess cofactor, and studies of activation no evidence of optic atrophy or retinitis pigmentosa. He could not failed to implicate a soluble inhibitor, abnormal binding of co-turn over, sit up. hold his head up, follow, or transfer objects. His factors, or defective activation as causes of the reduced enzyme posture was dystonic with continual choreoathetoid movements. activitv.He tended to hold his muscles rigidly but was profoundly ~h~" data are consistent an inherited defect in the second hypotonic when he relaxed. There were bilateral extensor plantar enzyme of the pyruvate dehydrogenase complex, lipoate acetyl-reflexes. The deep tendon reflexes were normal to slightly in...

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