PEPCK is a key enzyme in gluconeogenesis.
It catalyzes the conversion of oxaloacetate to phosphoenolpyruvate.
PEPCK deficiency has been described both as a mitochondrial (OMIM 261650)
and as a cytosolic (OMIM 261680) enzyme deficiency, encoded by two
distinct genes. The disease has been reported in only a few cases all
are questionable, with no molecular confirmation. The clinical features
are heterogeneous, with hypoglycemia, lactic acidemia, hepatomegaly,
hypotonia, developmental delay, and failure to thrive as the major
manifestations. Hepatic and renal dysfunction may be present. The
diagnosis is based on the reduced activity of PEPCK in liver, fibroblasts,
or lymphocytes. Fibroblasts and lymphocytes are not suitable for
diagnosing the cytosolic form of PEPCK deficiency, because these
tissues possess only mitochondrial PEPCK. To avoid hypoglycemia,
patients should be treated with slow-release carbohydrates such
as cornstarch, and fasting should be avoided.