Ribose-5-phosphate isomerase deficiency

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Ribose-5-phosphate isomerase deficiency
Classification and external resources
OMIM 608611

Ribose-5-phosphate isomerase deficiency (RPI deficiency, OMIM #608611) is a human disorder caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase. With a single diagnosed patient over a 27-year period, RPI deficiency is currently the rarest disease in the world.[1]


The affected boy was born in 1984 and diagnosed by MRI as suffering from a white matter disease (leukoencephalopathy). Analysis of SPECT profiles indicated an increase in the polyols arabitol, ribitol and erithritol.[2] This discovery later led to the identification of the disease-causing mutations, a premature stop codon and a missense mutation in the RPI gene.[3]


Since the report of this first case in 1999, no further patients have been diagnosed. In the search for an explanation for this rarity, it has been found that the patient has a seldom-seen allelic combination.[1] One allele is a non-functional null allele, while the other encodes for a partially active enzyme. Furthermore, the partially functional allele has expression deficits that depend on the cell type in which it is expressed. Therefore , some of the patient's cells have a considerable amount of RPI activity, whereas others do not.

The molecular cause of the pathology is not fully understood. One hypothesis is that ribose-5-phosphate may lack for RNA synthesis; another possibility is that the accumulation of D-ribitol and D-arabitol may be toxic.


  1. ^ van der Knaap, M. S.; Wevers, R. A.; Struys, E. A.; Verhoeven, N. M.; Pouwels, P. J.; Engelke, U. F.; Feikema, W.; Valk, J.; Jakobs, C. (1999). "Leukoencephalopathy associated with a disturbance in the metabolism of polyols". Ann. Neurol. 46 (6): 925–28. doi:10.1002/1531-8249(199912)46:6<925::aid-ana18>3.0.co;2-j. PMID 10589548. 
  2. ^ Huck, J. H.; Verhoeven, N. M.; Struys, E. A.; Salomons, G. S.; Jakobs, C.; van der Knaap, M. S. (2004). "Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy". Am. J. Hum. Genet. 74 (4): 745–51. doi:10.1086/383204. PMC 1181951Freely accessible. PMID 14988808.