Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy

Am J Hum Genet. 2004 Apr;74(4):745-51. doi: 10.1086/383204. Epub 2004 Feb 25.


The present article describes the first patient with a deficiency of ribose-5-phosphate isomerase (RPI) (Enzyme Commission number who presented with leukoencephalopathy and peripheral neuropathy. 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. Recently, we described a patient with liver cirrhosis and abnormal polyol levels in body fluids, related to a deficiency of transaldolase, another enzyme in the PPP. RPI is the second known inborn error in the reversible phase of the PPP, confirming that defects in pentose and polyol metabolism constitute a new area of inborn metabolic disorders.

MeSH terms

  • Aldose-Ketose Isomerases / deficiency*
  • Aldose-Ketose Isomerases / genetics*
  • Base Sequence
  • Carbohydrates / blood
  • Carbohydrates / cerebrospinal fluid
  • Carbohydrates / urine
  • Fibroblasts
  • Humans
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics
  • Molecular Sequence Data
  • Nervous System Diseases / enzymology*
  • Nervous System Diseases / genetics*
  • Pentose Phosphate Pathway / genetics*
  • Sugar Alcohols / blood
  • Sugar Alcohols / cerebrospinal fluid
  • Sugar Alcohols / urine


  • Carbohydrates
  • Sugar Alcohols
  • Aldose-Ketose Isomerases
  • ribosephosphate isomerase

Associated data

  • RefSeq/NM_144563