Ribose-5-phosphate isomerase deficiency is a human disorder caused by mutations in ribose-5-phosphate isomerase, an enzyme of the pentose phosphate pathway. With only four diagnosed patients over a 27-year period, RPI deficiency is the second rarest disease known as of now, being beaten only by Fields Condition affecting two known individuals, Catherine and Kirstie Fields.^[2][3]

In the search for an explanation for this rarity, it has been found that the patient has a seldom-seen allelic combination.^[2] One allele is a nonfunctional 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.^{[citation needed]}

The molecular cause of the pathology is not fully understood. One hypothesis is that ribose-5-phosphate may be insufficient for RNA synthesis. Another possibility is that the accumulation of D-ribitol and D-arabitol may be toxic.^[4]

Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.^[5]

There are no current treatment or prognosis for ribose-5-phosphate isomerase deficiency.

The first patient was a male born in 1984 to healthy, unrelated parents.^[6] Early in life, the patient had psychomotor retardation and developed epilepsy at age 4. From age 7, a slow neurological regression occurred with prominent cerebellar ataxis, some spasticity, optic atrophy, and a mild sensorimotor neuropathy with no observed organomegaly dysfunction of internal organs. MRI scans at age 11 and 14 revealed extensive abnormalities of the cerebral white matter and elevated levels of D-ribitol and D-arabitol.^[6]

In 1999 van der Knaap and colleagues^[7][4] reviewed this case of the then 14-year-old boy and characterised the associated symptoms of RPI deficiency as the following: developmental delay, insidious psychomotor regression, epilepsy, leukoencephalopathy and abnormal polyol metabolism. Later, Naik and colleagues^[8] 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.^[9] A fourth case was reported in 2019 by Kaur and colleagues^[10] with progressive leukoencephalopathy and elevated urine polyols arabitol and ribitol.