Medicine:Ribose-5-phosphate isomerase deficiency
| Ribose-5-phosphate isomerase deficiency | |
|---|---|
| Other names | RPI deficiency[1] |
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 three individuals, Catherine and Kirstie Fields and Pavle Milović.[2][3]
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 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]
Diagnosis
Symptoms include optic atrophy, nystagmus, cerebellar ataxia, seizures, spasticity, psychomotor retardation, leukoencephalopathy and global developmental delay.[5]
Treatment
There are no current treatment or prognosis for ribose-5-phosphate isomerase deficiency.
History
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.
References
- ↑ "OMIM Entry - # 608611 - RIBOSE 5-PHOSPHATE ISOMERASE DEFICIENCY". http://omim.org/entry/608611.
- ↑ 2.0 2.1 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. PMID 20499043. https://research.vumc.nl/en/publications/5b80fa40-596c-4de8-acf2-5374a1d878a0.
- ↑ Dalling, Robert (2017-02-10). "These twins are 'trapped' in their living room as work plans stall" (in en). http://www.walesonline.co.uk/news/wales-news/fields-twins-trapped-living-room-12641893.
- ↑ 4.0 4.1 "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. April 2004. doi:10.1086/383204. PMID 14988808.
- ↑ "Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". http://www.malacards.org/card/ribose_5_phosphate_isomerase_deficiency.
- ↑ 6.0 6.1 Huck, Jojanneke H. J.; Verhoeven, Nanda M.; Struys, Eduard A.; Salomons, Gajja S.; Jakobs, Cornelis; van der Knaap, Marjo S. (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): 745–751. doi:10.1086/383204. ISSN 0002-9297. PMID 14988808.
- ↑ "Leukoencephalopathy associated with a disturbance in the metabolism of polyols". Annals of Neurology 46 (6): 925–8. December 1999. doi:10.1002/1531-8249(199912)46:6<925::aid-ana18>3.0.co;2-j. PMID 10589548.
- ↑ "Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy". Neurology 89 (11): 1195–1196. September 2017. doi:10.1212/WNL.0000000000004361. PMID 28801340.
- ↑ "Further Delineation of Ribose-5-phosphate Isomerase Deficiency: Report of a Third Case". Journal of Child Neurology 33 (12): 784–787. October 2018. doi:10.1177/0883073818789316. PMID 30088433.
- ↑ Kaur, Parneet; Wamelink, Mirjam M.C.; Van Der Knaap, Marjo S.; Girisha, Katta Mohan; Shukla, Anju (2019-08-01). "Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA" (in en). European Journal of Medical Genetics 62 (8): 103708. doi:10.1016/j.ejmg.2019.103708. ISSN 1769-7212. PMID 31247379. https://www.sciencedirect.com/science/article/abs/pii/S1769721218305822.
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