Ribose-5-Phosphate Isomerase Deficiency: A Review of Pathogenesis, Clinical Diagnosis, and Management

Abstract

Ribose-5-phosphate isomerase deficiency (RPID) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the RPIA gene, which encodes the enzyme ribose-5-phosphate isomerase (RPI). This enzyme plays a crucial role in the non-oxidative phase of the pentose phosphate pathway (PPP), catalyzing the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate. The condition was first identified in 1999, and to date, only four cases have been documented worldwide, making it one of the rarest known genetic disorders. RPID manifests through various neurological symptoms, including developmental delay, psychomotor impairment, Leukoencephalopathy, seizures, nystagmus, optic atrophy, cerebellar ataxia, and spasticity. The pathophysiology involves impaired interconversion of pentose sugars, leading to abnormal accumulation of polyols such as arabitol and ribitol in brain tissue. Diagnosis typically relies on multiple approaches, including analysis of polyols in plasma, cerebrospinal fluid, and urine, brain proton magnetic resonance spectroscopy, and measurement of sugar-phosphate intermediates in fibroblasts or lymphoblasts. Currently, there is no targeted treatment for RPI deficiency, and management focuses on alleviating symptoms. However, ongoing research aims to develop targeted therapies through structural and genomic analysis of RPI. This condition underscores the critical role of PPP in cellular function and highlights potential areas for future therapeutic intervention in metabolic and genetic disorders.