Ribose-5-phosphate isomerase deficiency
Ribose-5-phosphate isomerase deficiency | |
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Other names | RPI 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]
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.
Diagnosis
Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.[3]
Treatment
There is no current treatment as well as prognosis for ribose-5-phosphate isomerase deficiency.
History
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]
References
- ^ "OMIM Entry - # 608611 - RIBOSE 5-PHOSPHATE ISOMERASE DEFICIENCY". omim.org. Retrieved 16 March 2019.
- ^ a b 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.
- ^ "Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2018-03-05.
- ^ 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. doi:10.1002/1531-8249(199912)46:6<925::AID-ANA18>3.0.CO;2-J. PMID 10589548.
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: CS1 maint: multiple names: authors list (link) - ^ 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.
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: CS1 maint: multiple names: authors list (link) - ^ 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 (11): 1–2. doi:10.1212/WNL.0000000000004361. PMID 28801340.
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: CS1 maint: multiple names: authors list (link) - ^ 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