RPI deficiency: scoping review of genotype-phenotype correlations and diagnostic markers
https://doi.org/10.5281/zenodo.19672245
Keywords:
erros inatos do metabolismo, via das pentoses-fosfato, leucoencefalopatia, biomarcadores, neuroimagem, RPIAAbstract
This study aimed to map the clinical and translational literature on ribose-5-phosphate isomerase deficiency, focusing on reported human cases, diagnostic biomarkers, and recurrent clinical-radiological patterns. A scoping review was conducted through structured searches in indexed biomedical literature followed by reference tracking and narrative synthesis. Retrieved evidence showed an extremely small documentary corpus, comprising four confirmed affected individuals in primary clinical publications, along with molecular characterization studies and ancillary biochemical reports. The core phenotype was early-onset progressive leukoencephalopathy associated with developmental delay or regression and, in some patients, peripheral neuropathy, epilepsy, and visual impairment. The most robust biomarkers were increased ribitol and D-arabitol in urine and other body fluids, cerebral polyol peaks on magnetic resonance spectroscopy, and demonstration of deficient enzyme activity or bi-allelic RPIA variants. It is concluded that diagnosis depends less on a highly specific syndromic pattern and more on combining metabolic suspicion, targeted polyol testing, and molecular confirmation
References
BONKOWSKY, Joshua L.; KELLER, Stephanie. Leukodystrophies in children: diagnosis, care, and treatment. Pediatrics, [S. l.], v. 148, n. 3, e2021053126, 2021. DOI: 10.1542/peds.2021-053126. Disponível em: [https://doi.org/10.1542/peds.2021-053126]. Acesso em: 21 dez. 2025.
BROOKS, Susan Sklower et al. Further delineation of ribose-5-phosphate isomerase deficiency: report of a third case. Journal of Child Neurology, [S. l.], v. 33, n. 12, p. 784-787, 2018. DOI: 10.1177/0883073818789316. Disponível em: [https://doi.org/10.1177/0883073818789316]. Acesso em: 21 dez. 2025.
HUCK, Jojanneke H. J. et al. Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy. American Journal of Human Genetics, [S. l.], v. 74, n. 4, p. 745-751, 2004. DOI: 10.1086/383204. Disponível em: [https://doi.org/10.1086/383204]. Acesso em: 21 dez. 2025.
KAUR, Parneet et al. Confirmation of a rare genetic leukoencephalopathy due to a novel bi-allelic variant in RPIA. European Journal of Medical Genetics, [S. l.], v. 62, n. 8, 103708, 2019. DOI: 10.1016/j.ejmg.2019.103708. Disponível em: [https://doi.org/10.1016/j.ejmg.2019.103708]. Acesso em: 21 dez. 2025.
KOY, Anne et al. Urinary excretion of pentose phosphate pathway-associated polyols in early postnatal life. Neonatology, [S. l.], v. 95, n. 3, p. 256-261, 2009. DOI: 10.1159/000167789. Disponível em: [https://doi.org/10.1159/000167789]. Acesso em: 21 dez. 2025.
MOOLENAAR, Sytske H. et al. In vivo and in vitro NMR spectroscopy reveal a putative novel inborn error involving polyol metabolism. NMR in Biomedicine, [S. l.], v. 14, n. 3, p. 167-176, 2001. DOI: 10.1002/nbm.690. Disponível em: [https://doi.org/10.1002/nbm.690]. Acesso em: 21 dez. 2025.
NAIK, Neeta et al. Rare case of ribose 5 phosphate isomerase deficiency with slowly progressive leukoencephalopathy. Neurology, [S. l.], v. 89, n. 11, p. 1195-1196, 2017. DOI: 10.1212/WNL.0000000000004361. Disponível em: [https://doi.org/10.1212/WNL.0000000000004361]. Acesso em: 21 dez. 2025.
PETERS, Micah D. J. et al. Updated methodological guidance for the conduct of scoping reviews. JBI Evidence Synthesis, [S. l.], v. 18, n. 10, p. 2119-2126, 2020. DOI: 10.11124/JBIES-20-00167. Disponível em: [https://doi.org/10.11124/JBIES-20-00167]. Acesso em: 21 dez. 2025.
SHAYOTA, Brian J. et al. Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway. Molecular Genetics and Metabolism, [S. l.], v. 131, n. 1-2, p. 147-154, 2020. DOI: 10.1016/j.ymgme.2020.07.013. Disponível em: [https://doi.org/10.1016/j.ymgme.2020.07.013]. Acesso em: 21 dez. 2025.
STONE, V. et al. Polyols accumulated in ribose-5-phosphate isomerase deficiency increase mitochondrial superoxide production and improve antioxidant defenses in rats’ prefrontal cortex. International Journal of Developmental Neuroscience, [S. l.], v. 37, p. 21-25, 2014. DOI: 10.1016/j.ijdevneu.2014.06.009. Disponível em: [https://doi.org/10.1016/j.ijdevneu.2014.06.009]. Acesso em: 21 dez. 2025.
TRICCO, Andrea C. et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Annals of Internal Medicine, [S. l.], v. 169, n. 7, p. 467-473, 2018. DOI: 10.7326/M18-0850. Disponível em: [https://doi.org/10.7326/M18-0850]. Acesso em: 21 dez. 2025.
VAN DER KNAAP, Marjo S. et al. Leukoencephalopathy associated with a disturbance in the metabolism of polyols. Annals of Neurology, [S. l.], v. 46, n. 6, p. 925-928, 1999. DOI: 10.1002/1531-8249(199912)46:6<925::AID-ANA18>3.0.CO;2-J. Disponível em: [https://doi.org/10.1002/1531-8249(199912)46:6<925::AID-ANA18>3.0.CO;2-J]. Acesso em: 21 dez. 2025.
VAN DER KNAAP, Marjo S.; SCHIFFMANN, Raphael; MOCHEL, Fanny; WOLF, Nicole I. Diagnosis, prognosis, and treatment of leukodystrophies. The Lancet Neurology, [S. l.], v. 18, n. 10, p. 962-972, 2019. DOI: 10.1016/S1474-4422(19)30143-7. Disponível em: [https://doi.org/10.1016/S1474-4422(19)30143-7]. Acesso em: 21 dez. 2025.
WAMELINK, Mirjam M. C. et al. Analysis of polyols in urine by liquid chromatography-tandem mass spectrometry: a useful tool for recognition of inborn errors affecting polyol metabolism. Journal of Inherited Metabolic Disease, [S. l.], v. 28, n. 6, p. 951-963, 2005. DOI: 10.1007/s10545-005-0233-4. Disponível em: [https://doi.org/10.1007/s10545-005-0233-4]. Acesso em: 21 dez. 2025.
WAMELINK, Mirjam M. C.; STRUYS, Eduard A.; JAKOBS, Cornelis. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. Journal of Inherited Metabolic Disease, [S. l.], v. 31, n. 6, p. 703-717, 2008. DOI: 10.1007/s10545-008-1015-6. Disponível em: [https://doi.org/10.1007/s10545-008-1015-6]. Acesso em: 21 dez. 2025.
WAMELINK, Mirjam M. C. et al. The difference between rare and exceptionally rare: molecular characterization of ribose 5-phosphate isomerase deficiency. Journal of Molecular Medicine, [S. l.], v. 88, n. 9, p. 931-939, 2010. DOI: 10.1007/s00109-010-0634-1. Disponível em: [https://doi.org/10.1007/s00109-010-0634-1]. Acesso em: 21 dez. 2025.
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