Ribose-5-phosphate isomerase deficiency

Ribose-5-phosphate isomerase deficiency is a human disorder caused by mutations in the pentose phosphate pathway enzyme ribose-5-phosphate isomerase. With only three diagnosed patients over a 27-year period, RPI deficiency is currently the rarest disease in the world.

Mechanism

In the search for an explanation for this rarity, it has been found that the patient has a seldom-seen allelic combination. 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.

Diagnosis

Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.

Treatment

There is no current treatment as well as prognosis for ribose-5-phosphate isomerase deficiency.

History

In 1999 van der Knaap and colleagues described a 14-year-old boy with developmental delay, insidious psychomotor regression, epilepsy, leukoencephalopathy and abnormal polyol metabolism. Later, Naik and colleagues reported a second case, an 18-year-old man with seizures, psychomotor regression and diffuse white matter abnormality. A third case was reported in 2018 by Sklower Brooks and colleagues, a child with neonatal onset leukoencephalopathy and psychomotor delays.

External links

Classification	OMIM: 608611
External resources	Orphanet: 440706