Rare Genetic Diseases: RPI Deficiency

Ribose-5-phosphate isomerase deficiency is considered the rarest disease in the world, with only three diagnosed cases. The disease was first observed in 1999 in a 14-year old boy with delayed development, epilepsy, and abnormal polyol metabolism.

The characteristic symptoms of RPI include optic atrophy (damaged optic nerve), nystagmus (involuntary eye movement), seizures, developmental delay. Furthermore, the patients may suffer from leukoencephalopathy (disease of all of the brain white matter). Spasticity (altered skeletal muscle performance) and psychomotor retardation occur often in patients with RPI.

The disease is caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase. This occurs due to a rare allelic combination. While one allele encodes for a partial activity of enzymes, the other one is a non-functional null allele.

The functional allele has expression deficits that depend on the cell type in which it is expressed. Thus, some patients have higher Rpi activity. On the molecular level, the disease is not fully understood yet. However, it is hypothesized that the ribose-5-phosphate lacks in RNA synthesis.

Currently, there is no treatment for RPI disease. Due to the low number of known cases, life expectancy has not been established.