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 one unknown person.[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 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.[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 is 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 four. From age seven, 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 elevated levels of the 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". 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. S2CID 10870492.
- ^ Dalling, Robert (2017-02-10). "These twins are 'trapped' in their living room as work plans stall". WalesOnline. Retrieved 2021-07-31.
- ^ a b 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.
- ^ a b 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. PMC 1181951. PMID 14988808.
- ^ 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. S2CID 43743595.
- ^ 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. S2CID 9554949.
- ^ 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. S2CID 51936427.
- ^ 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". European Journal of Medical Genetics. 62 (8): 103708. doi:10.1016/j.ejmg.2019.103708. ISSN 1769-7212. PMID 31247379. S2CID 195760193.