Ribose-5-phosphate isomerase deficiency
Other namesRPI 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 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.

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

  1. "OMIM Entry - # 608611 - RIBOSE 5-PHOSPHATE ISOMERASE DEFICIENCY". omim.org. Retrieved 16 March 2019.
  2. Dalling, Robert (2017-02-10). "These twins are 'trapped' in their living room as work plans stall". WalesOnline. Retrieved 2021-07-31.
  3. 1 2 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.
  4. "Ribose 5-Phosphate Isomerase Deficiency disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials". www.malacards.org. Retrieved 2018-03-05.
  5. 1 2 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.