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About 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 generates NADH. One of the metabolites, ribose-5-phosphate, 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 2 recently described enzyme deficiencies: transaldolase deficiency and ribose-5-phosphate isomerase deficiency.


Essential pentosuria (Online Mendelian Inheritance in Man [MIM] no. 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 following a urine test for reducing substances. No treatment is required.


Transaldolase deficiency (MIM no. 606003) affects the nonoxidative branch of the hexose monophosphate pathway. This rare, multisystemic disease has been reported in the literature in less than 30 patients. Patients present in early infancy with various degrees of hepatic, cardiac, and renal involvement. Hepatosplenomegaly and liver dysfunction, along with pancytopenia, are the most common clinical features. Patients also exhibit cutis laxa and dysmorphic facial features. Occasionally, antenatal symptoms of hydrops fetalis and oligohydramnios are present as well. In the most recently reported case, antenatal ultrasound revealed hyperechogenic bowel, and the patient required surgical intervention for intestinal obstruction at birth.

Transaldolase deficiency is detected through the listed clinical features and biochemical abnormalities. Urine and plasma biochemistry reveals elevated levels of D-arabitol, ribitol, and erythritol, among others. Enzyme assay of low transaldolase activity in the lymphoblasts/fibroblasts and DNA sequencing confirm the diagnosis. Currently, there is no treatment available for this deficiency; however, there is ongoing investigation of N-acetylcysteine therapy in a mouse model.


To date, only 1 case of ribose-5-phosphate isomerase deficiency (MIM no. 608611) has been reported. The affected male had psychomotor retardation from early in life and developed epilepsy at 4 years of age. Thereafter, a slow neurologic regression developed with prominent cerebellar ataxia, some spasticity, optic atrophy, and a mild sensorimotor neuropathy. Magnetic resonance imaging of the brain at ages 11 and 14 years showed extensive abnormalities of the cerebral white matter. Proton magnetic resonance spectroscopy 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 with transaldolase deficiency, and there is a notable accumulation of pentitols in the central nervous system; however, the pathophysiology of the disorder is not understood. Enzyme assays in cultured fibroblasts showed deficient ribose-5-phosphate isomerase ...

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