Ribose-5-phosphate isomerase (EC 5.3.1.6) deficiency is an inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. Proton magnetic resonance spectroscopy of the brain revealed highly elevated levels of the polyols ribitol and D-arabitol, which were subsequently also found in high concentrations in body fluids. Deficient activity of RPI, one of the pentose-phosphate-pathway (PPP) enzymes, was demonstrated in fibroblasts. RPI gene-sequence analysis revealed a frameshift and a missense mutation (PMID:14988808).
Huck et al. (2004) described a patient with a deficiency of ribose 5-phosphate isomerase who presented with leukoencephalopathy and peripheral neuropathy. Huck et al. (2004) noted that children with neurologic deficits of central origin often demonstrate white matter abnormalities ...Huck et al. (2004) described a patient with a deficiency of ribose 5-phosphate isomerase who presented with leukoencephalopathy and peripheral neuropathy. Huck et al. (2004) noted that children with neurologic deficits of central origin often demonstrate white matter abnormalities on MRI. Often a specific diagnosis is not possible despite extensive investigations. Their patient had psychomotor retardation from early in life and developed epilepsy at age 4 years. After age 7 years, a slow neurologic regression occurred with prominent cerebellar ataxia, some spasticity, optic atrophy, and a mild sensorimotor neuropathy. Neither organomegaly nor dysfunction of the internal organs was present. Extensive abnormalities of the cerebral white matter were demonstrated by MRI of the brain at ages 11 and 14 years. Proton magnetic resonance spectroscopy of the brain showed highly elevated abnormal peaks that were identified as representing pentitols ribitol and D-arabitol. Deficient activity of RPI, one of the pentose phosphate pathway enzymes, was demonstrated in fibroblasts. Deficiency of transaldolase (602063), another enzyme in the pentose phosphate pathway, had previously been demonstrated in a patient with liver cirrhosis and abnormal polyol levels in body fluids. RPI deficiency represented the second instance of an inborn error in the reversible phase of the pentose phosphate pathway, confirming that defects in pentose and polyol metabolism constitute a group of inborn metabolic disorders
By sequence analysis of the RPI gene in a patient with deficiency of ribose 5-phosphate isomerase, Huck et al. (2004) demonstrated compound heterozygosity for a frameshift (180430.0001) and a missense (180430.0002) mutation.