Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial

Clinical Features

In 2 unrelated children, Hommes et al. (1976) observed hypoglycemia and liver impairment, with deficiency of PEPCK (614095) in liver tissue taken immediately after death. Massive fatty deposition in liver and kidneys was found at autopsy. Fiser et al. (1974) also observed hypoglycemia caused by deficiency of PEPCK. Other enzymatic causes of hypoglycemia include glucose-6-phosphatase deficiency (232200), fructose-1,6-diphosphatase deficiency (229700), and pyruvate carboxylase deficiency (266150).

Robinson et al. (1980) studied skin fibroblast cultures from 40 pediatric cases of lactic acidosis. They found one case in which mitochondrial activity of phosphoenolpyruvate carboxykinase was 6% of normal.

See 261680 for a discussion of cytosolic PCK deficiency.

History

Phosphoenolpyruvate carboxykinase can be measured in fibroblasts, which are said (Clayton et al., 1986) to contain only mitochondrial PEPCK. Clayton et al. (1986) reported this disorder in a female child who died of liver failure at 6 months and probably in her brother who died a crib death at 4 weeks. Leonard et al. (1991) studied the next child in this family, a boy who developed a similar illness with liver failure. PEPCK activity in leukocytes and fibroblasts was normal, however, leading Leonard et al. (1991) to conclude that the primary defect in this family does not reside in this enzyme. Subsequent studies of a third affected child in this family by Bodnar et al. (1993) suggested that the sibs suffered from the mitochondrial DNA depletion syndrome (251880) and that this depletion is controlled by the nuclear genome.