Ribose-5-phosphate isomerase deficiency

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, RPI deficiency is currently thought to be 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 erithrol.^[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 suffers from a seldom-seen allelic combination.^[4] 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.

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