DIAGNOSIS, CLINICAL ASPECTS AND THERAPEUTIC MANAGEMENT OF ORNITHINE TRANSCARBAMYLASE DEFICIENCY: A SYSTEMATIC REVIEW

Abstract

Introduction:Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, characterized by toxic ammonia accumulation caused by mutations in the OTC gene. This condition can lead to severe neurological and metabolic complications, making early diagnosis crucial for appropriate clinical management.Objective:To analyze the clinical, diagnostic, and therapeutic aspects of ornithine transcarbamylase deficiency based on evidence published between 2020 and 2025.Method:This systematic review followed the PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251067439). Thirteen original studies from PubMed, SciELO, Scopus, Science Direct, Medline, LILACS, and BVS databases were included, addressing clinical manifestations, diagnostic methods, and therapeutic strategies.Results:The studies highlighted the effectiveness of neonatal screening through tandem mass spectrometry (MS/MS) and enzymatic assays, the significance of genotype–phenotype correlations, and the role of liver transplantation in metabolic stabilization and survival improvement (>95%). Female carriers presented underestimated clinical risks, especially during pregnancy. Recent gene therapy trials (DTX301) demonstrated promising safety and efficacy outcomes.Conclusion:Current evidence shows significant progress in the diagnostic and therapeutic management of OTC deficiency. However, access inequality and the lack of standardized protocols remain challenges. Strengthening neonatal screening, expanding genetic counseling, and developing innovative molecular therapies represent promising strategies to improve the prognosis and quality of life of affected individuals.