Ribose-5-phosphate isomerase deficiency
|Ribose-5-phosphate isomerase deficiency|
Ribose-5-phosphate isomerase deficiency (Rpi deficiency, OMIM #608611) 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 one of the rarest diseases in the world.
In the search for an explanation for this rarity, it has been found that the patient has a seldom-seen allelic combination. 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.
There is no current treatment as well as prognosis for Ribose-5-Phophate Isomerase deficiency.
In 1999 van der Knaap and colleagues   described a 14-year-old boy with developmental delay, insidious psychomotor regression, epilepsy, leukoencephalopathy and abnormal polyol metabolism. Later, Naik and colleagues  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.
- "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. Leukoencephalopathy associated with a disturbance in the metabolism of polyols.Ann Neurol. 1999;46(6):925-928.
- 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. PMC 1181951. PMID 14988808. doi:10.1086/383204.
- Naik N, Shah A, Wamelink MMC, van der Knaap MS, Hingwala D. Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy. Neurology. 2017;89:1-2.
- 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