Ribose-5-phosphate isomerase (RPI) deficiency, is a genetic disorder caused by mutations in the RPIA gene that codes for RPI. RPI is an enzyme that is involved in the pentose phosphate pathway as part of carbohydrate degradation. It reversibly converts D-ribulose 5-phosphate into D-ribose 5-phosphate. In the case of this disorder, RPI functions partially in tissues, because if the gene was simply non-functional, it would likely be lethal. This means that a specific type of mutation needs to occur for this disorder to occur, leading to it being the rarest disease in the world, with only three confirmed cases. In the first known case, the patient had one allele containing a frameshift mutation, which led to a truncated protein, while the other allele contained a missense mutation. This combination meant that activity of RPI was found to vary across tissues and cell types. Characteristics of the RPI deficiency include higher ribitol and arabitol levels in a metabolic profile, as well as differences in polyol profiles. There are other symptoms, including leukoencephalopathy and neuropathy, which may be caused by a toxic accumulation of ribitol and arabitol, or a potential lack of ribose-5-phosphate in RNA synthesis.

Ribose-5-phosphate Isomerase Deficiency References

Pentose Phosphate Pathway References