Ribose-5-phosphate isomerase deficiency

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Ribose-5-phosphate isomerase deficiency
Other namesRPI deficiency[1]

Ribose-5-phosphate isomerasedeficiency 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.[2]


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 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.


Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.[3]


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


In 1999 van der Knaap and colleagues[4][5] described a 14-year-old boy with developmental delay, insidious psychomotor regression, epilepsy, leukoencephalopathy and abnormal polyol metabolism. Later, Naik and colleagues[6] 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.[7]


  1. ^ "OMIM Entry - # 608611 - RIBOSE 5-PHOSPHATE ISOMERASE DEFICIENCY". omim.org. Retrieved 16 March 2019.
  2. ^ "Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2018-03-05.
  3. ^ van der Knapp MS, Wevers RA, Struys EA; et al. (1999). "Leukoencephalopathy associated with a disturbance in the metabolism of polyols". Ann Neurol. 46 (6): 925–928.CS1 maint: multiple names: authors list (link)
  4. ^ Huck J. H. J., Verhoeven N. M., Struys E. A., Salomons G. S., Jakobs C., Van Der Knaap M. S. (2004). "Ribose-5-Phosphate Isomerase Deficiency: New Inborn Error in the Pentose Phosphate Pathway Associated with a Slowly Progressive Leukoencephalopathy". The American Journal of Human Genetics. 74 (4): 745–751. doi:10.1086/383204. PMC 1181951. PMID 14988808.CS1 maint: multiple names: authors list (link)
  5. ^ Naik N, Shah A, Wamelink MMC, van der Knaap MS, Hingwala D (2017). "Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy". Neurology. 89: 1–2.CS1 maint: multiple names: authors list (link)
  6. ^ Sklower Brooks S, Anderson S, Bhise V, Botti C. Further Delineation of Ribose-5-phosphate Isomerase Deficiency: Report of a Third Case, Journal of Child Neurology: First Published August 10, 2018 Journal of Child Neurology. https://doi.org/10.1177/0883073818789316

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