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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.

1About 90% of glucose metabolism in the body occurs via the glycolytic pathway, and the remaining 10% via the hexose monophosphate pathway. The hexose monophosphate shunt leads to formation of pentoses and provides NADH. One of the metabolites is ribose-5-phosphate, which is used in the biosynthesis of ribonucleotides and deoxyribonucleotides. Through the transketolase and transaldolase reactions, the pentose phosphates can be converted back to fructose-6-phosphate and glucose-6-phosphate. The congenital abnormalities in pentose metabolism include a benign pentosuria and two recently described enzyme deficiencies: transaldolase deficiency and ribose-5-phosphate isomerase deficiency.

Essential pentosuria (OMIM 260800) is a benign disorder encountered mainly in Ashkenazi Jews and is inherited as an autosomal recessive trait. The urine contains L-xylulose, which is excreted in increased amounts because of a block in the conversion of L-xylulose to xylitol due to xylitol dehydrogenase deficiency. The condition is usually discovered accidentally in a urine test for reducing substances. No treatment is required.

To date, the literature has reported that only about 10 patients are affected with transaldolase deficiency (OMIM 606003). Symptoms include hydrops foetalis with oligoamnios, dysmorphia, severe recurrent anemia, hepatosplenomegaly, and variable liver, renal, or cardiac involvement in early infancy leading to early death in infancy or to gradual improvement and adult cirrhosis. Biochemical abnormalities revealed elevated levels of arabitol, ribitol, and erythritol in the urine. Enzyme assay in the lymphoblasts/fibroblasts demonstrated low transaldolase activity, which was confirmed by the identification mutations in the transaldolase gene.

Only one case of ribose-5-phosphate isomerase deficiency (OMIM 608611) has been reported so far. The affected male had psychomotor retardation from early in life and developed epilepsy at 4 years of age. Thereafter, a slow neurological regression developed with prominent cerebellar ataxia, some spasticity, optic atrophy, and a mild sensorimotor neuropathy. MRI of the brain at ages 11 and 14 years showed extensive abnormalities of the cerebral white matter. Proton MRS of the brain revealed elevated levels of ribitol and D-arabitol. These pentitols were also increased in urine and plasma, which is similar to the patient found in transaldolase deficiency. Enzyme assays in cultured fibroblasts showed deficient ...

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