PYRUVATE-CARBOXYLASE DEFICIENCY AND LACTIC-ACIDOSIS IN A RETARDED-CHILD WITHOUT LEIGHS DISEASE

A child with lactic acidosis, severe mental and developmental retardation and proximal renal tubular acidosis was presented. Biopsy and autopsy studies show severe hepatic, renal cortical and cerebral deficiencies in pyruvate carboxylase (EC 6.4.1.1) activity. The patient had 1.81 .+-. 0.20 units/g fresh wt at biopsy and 0.75 .+-. 0.07 units/g fresh wt hepatic pyruvate carboxylase activity at autopsy compared with 10.9, 11.3 and 9.5 units/g fresh weight in 2 autopsy and 1 biopsy controls, respectively. The patient''s renal cortical pyruvate carboxylase activity at autopsy was 0.008 .+-. 0.004 units/g fresh wt compared with 5.05 units/g in the autopsy control. The patient had no detectable (< 0.018 units/g fresh wt) cerebral pyruvate carboxylase activity at autopsy compared with 0.44, 0.53 and 0.695 units/g in the autopsy cerebrum of 1 human and 2 rhesus monkeys, respectively. Pyruvate dehydrogenase complex, phosphoenolpyruvate carboxykinase (PEPCK, EC 4.1.1.32), and fructose-1,6-bisphosphatase (EC 3.1.3.11) activities were in the normal range. The patient''s urine pH was above 7.9 when the total serum CO2 was greater than 7.8 mM. The patient was able to acidify the urine to pH 5.1 when the total serum CO2 was 1.6 mM. The neuropathologic examination of the brain at autopsy revealed no sign of Leigh''s disease, although developmental and degenerative lesions were observed. This is the 1st reported patient with a primary deficiency in hepatic, renal and cerebral pyruvate carboxylase deficiency in whom the neuropathologic lesions, distinct from those of Leigh''s disease and proximal renal tubular acidosis were both documented.