Liver transplantation for late-onset ornithine transcarbamylase deficiency:A case report

BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is an X-linked inherited disorder and characterized by marked elevation of blood ammonia.The goal of treatment is to minimize the neurological damage caused by hyperammonemia.OTCD can be cured by liver transplantation(LT).Post-transplant patients can discontinue anti-hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia.The neurological damage caused by hyperammonemia is almost irreversible.CASE SUMMARY An 11.7-year-old boy presented with headache,vomiting,and altered consciousness.The patient was diagnosed with late-onset OTCD.After nitrogen scavenging treatment and a protein-free diet,ammonia levels were reduced to normal on the third day of admission.Nevertheless,the patient remained in a moderate coma.After discussion,LT was performed.Following LT,the patient’s blood ammonia and biochemical indicators stabilized in the normal range,he regained consciousness,and his nervous system function significantly recovered.Two months after LT,blood amino acids and urine organic acids were normal,and brain magnetic resonance imaging showed a decrease in subcortical lesions.CONCLUSION LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy,and LT can be actively considered when early drug therapy is ineffective.

Hemizygous deletion in the OTC gene results in ornithine transcarbamylase deficiency:A case report

BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is a common ornithine cycle disorder,and OTC gene variation is the main pathogenic factor of this disease.This study explored and validated a variant in the OTC gene.CASE SUMMARY The neonate exhibited high blood ammonia,lactic acid,and homocysteine levels on the fifth day after birth.A novel deletion variant in the OTC gene[NM_000531.5,c.970_979delTTCCCAGAGG,p.Phe324GlnfsTer16]was uncovered by exome sequencing.The variant caused a protein-coding frameshift and resulted in early translation termination at the 16th amino acid after the variant site.CONCLUSION Our results provide a novel pathogenic variant in OTC and related clinical features for further OTCD screening and clinical consultation.

Genotype-Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update

Ornithine transcarbamylase （OTC） deficiency is an X-linked trait that accounts for nearly half of all inherited disorders of the urea cycle. OTC is one of the enzymes common to both the urea cycle and the bacterial arginine biosynthesis pathway; however, the role of OTC has changed over evolution. For animals with a urea cycle, defects in OTC can trigger hyperammonemic episodes that can lead to brain damage and death. This is the fifth mutation update for human OTC with previous updates reported in 1993, 1995, 2002, and 2006. In the 2006 update, 341 mutations were reported. This current update contains 417 disease-causing mutations, and also is the first report of this series to incorporate information about natural variation of the OTC gene in the general population through examination of publicly available genomic data and examination of phenotype/genotype correlations from patients participating in the Urea Cycle Disorders Consortium Longitudinal Study and the first to evaluate the suitability of systematic computational approaches to predict severity of disease associated with different types of OTC mutations.