Clinical and genetic analysis of five Chinese patients with urea cycle disorders

Zheng, Zhiyong; Lin, Yiming; Lin, Weihua; Zhu, Lin; Jiang, Min; Wang, Wenjun; Fu, Qingliu

doi:10.1002/mgg3.1301

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…With improvements in health care, the mortality in neonatal-onset cases has significantly decreased from previous reports of 50% [ 8 ] to 24% [ 7 ] nowadays. To date, there have been several studies of UCDs in China [ 9 – 11 ]. However, few focus on the relation between the clinical course, metabolomic profiling, molecular genetic of severe neonatal-onset types, and their survivals.…”

Section: Introductionmentioning

confidence: 99%

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients

Zhou¹,

Huang²,

et al. 2020

BioMed Research International

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During Jan. 2016–Dec. 2019, nine Chinese patients from eight unrelated families were diagnosed with neonatal-onset UCDs by targeted panel sequencing or whole-exome sequencing (WES). Their clinical manifestations, biochemical features, 180-day-age outcomes, and molecular genetic characteristics were reviewed retrospectively. NGS-based tests revealed 7 patients diagnosed with ornithine transcarbamylase deficiency (OTCD) and 2 with carbamoylphosphate synthetase I deficiency (CPS1D). The spectrum of the clinical presentation of nine affected individuals progressed from unspecific symptoms like poor feeding to somnolence, coma, and death. All patients presented with an acute hyperammonemia. The most robust metabolic pattern in OTCD was hyperglutaminemic hyperammonemia with high concentration of urine orotic acid, and it was reported in six patients. Of ten variants found on the OTC gene and CPS1 gene, 3 were novel: (c.176T>C (p.L59P)) in the OTC gene, c.2938G>A (p.G980S) and c.3734T>A (p.L1245H) in the CPS1 gene. There was a high mortality rate of 77.78% (7/9) for all the defects combined. An OTC-deficient male and a CPS1-deficient female survived from episodes of hyperammonemia. Although prompt recognition of UCD and the use of alternative pathway therapy in addition to provision of appropriate nutrition and dialysis improved survival, the overall outcomes for the neonatal-onset type are poor in China.

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Section: Introductionmentioning

confidence: 99%

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients

Zhou¹,

Huang²,

et al. 2020

BioMed Research International

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Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises

Chanvanichtrakool,

Schreiber,

Chen

et al. 2024

Pediatric Neurology

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Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China

Yuan,

Liu,

Chen

et al. 2023

Preprint

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BackgroundThis study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. MethodsThe clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 were analyzed retrospectively. ResultsFive boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. Five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all with hepatic impairment, and four with hepatic failure. Coagulopathy occurred in eight patients. Urinary orotic acid levels were elevated in all patients except in one who received blood purification therapy. Only six patients showed decreased serum citrulline levels. Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T>A(p.M56K). Despite active treatment, seven patients died, of whom five had early-onset disease. Three patients survived, and two underwent liver transplantation. ConclusionsThe clinical manifestations of OTCD lack specificity. Elevated blood ammonia is a diagnostic clue for OTCD, elevated urinary orotate is specific for its diagnosis, and genetic testing can help confirm the diagnosis. These two novel variants expand the mutational spectra of OTC, which may contribute to a better understanding of the clinical and genetic characteristics of patients with OTCD.

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Clinical and genetic analysis of five Chinese patients with urea cycle disorders

Cited by 4 publications

References 30 publications

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients

The Application of Next-Generation Sequencing (NGS) in Neonatal-Onset Urea Cycle Disorders (UCDs): Clinical Course, Metabolomic Profiling, and Genetic Findings in Nine Chinese Hyperammonemia Patients

Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises

Clinical characteristics and molecular genetic analysis of ten cases of ornithine carbamoyltransferase deficiency in southeastern China

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