Ribose-5-phosphate isomerase deficiency
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]
| Ribose-5-phosphate isomerase deficiency | |
|---|---|
| Other names | RPI deficiency[1] |
Mechanism
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.[3]
Diagnosis
Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.[4]
Treatment
There is no current treatment as well as prognosis for ribose-5-phosphate isomerase deficiency.
History
In 1999 van der Knaap and colleagues[5][3] 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]
References
- "OMIM Entry - # 608611 - RIBOSE 5-PHOSPHATE ISOMERASE DEFICIENCY". omim.org. Retrieved 16 March 2019.
- Wamelink, M. M.; Grüning, N. M.; Jansen, E. E.; Bluemlein, K.; Lehrach, H.; Jakobs, C.; Ralser, M. (2010). "The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency". J. Mol. Med. 88 (9): 931–39. doi:10.1007/s00109-010-0634-1. hdl:1871/34686. PMID 20499043. S2CID 10870492.
- Huck JH, Verhoeven NM, Struys EA, Salomons GS, Jakobs C, van der Knaap MS (April 2004). "Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy". American Journal of Human Genetics. 74 (4): 745–51. doi:10.1086/383204. PMC 1181951. PMID 14988808.
- "Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2018-03-05.
- van der Knaap MS, Wevers RA, Struys EA, Verhoeven NM, Pouwels PJ, Engelke UF, Feikema W, Valk J, Jakobs C (December 1999). "Leukoencephalopathy associated with a disturbance in the metabolism of polyols". Annals of Neurology. 46 (6): 925–8. doi:10.1002/1531-8249(199912)46:6<925::aid-ana18>3.0.co;2-j. PMID 10589548.
- Naik N, Shah A, Wamelink MC, van der Knaap MS, Hingwala D (September 2017). "Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy". Neurology. 89 (11): 1195–1196. doi:10.1212/WNL.0000000000004361. PMID 28801340.
- Brooks SS, Anderson S, Bhise V, Botti C (October 2018). "Further Delineation of Ribose-5-phosphate Isomerase Deficiency: Report of a Third Case". Journal of Child Neurology. 33 (12): 784–787. doi:10.1177/0883073818789316. PMID 30088433.