OBJECTIVETo analyze the clinical features, metabolic profiling and gene mutations of patients with ornithine transcarbamylase deficiency (OTCD) and explore the molecular pathogenesis of OTCD in order to provide a solution for molecular diagnostics and genetic counseling.

METHODSClinical data of 3 neonates were analyzed. The amino acids level in blood was analyzed with mass spectrum technology. PCR was used to amplify all the 10 exons of OTC gene. The PCR products were directly sequenced to detect the mutations.

RESULTSAll of the 3 cases had neonatal onset and showed poor reaction, feeding difficulty, convulsion and neonatal infection. Citrulline levels were significantly decreased. Case 1 had a missense mutation of Y183C. Case 2 showed a missense mutation of V339G in exon 10. And a missense mutations of W332S in exon 9 was detected in case 3.

CONCLUSIONAnalysis of OTC gene sequences can be used for the diagnosis of OTCD and screening of asymptomatic carriers. Mutation analysis is important for prenatal diagnosis of individuals with a positive family history and genetic counseling. The V339G and W332S mutations have been discovered for the first time. Patients with such mutations may have onset of the disease during neonatal period.

Humans ; Male ; Mutation ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; genetics ; metabolism

OBJECTIVETo detect potential mutations of OTC gene in a male infant affected with ornithine transcarbamylase deficiency.

METHODSGenomic DNA were isolated from peripheral blood samples of family members and 100 healthy individuals. Potential mutations of the 10 exons of OTC gene were screened with PCR and Sanger sequencing.

RESULTSA homozygous missense mutation c.917G>C in exon 9, which results in p.R306T, was identified in the infant. Sequencing of the mother and two female members of the family indicated a heterozygous status for the same mutation. The same mutation was not found in other members of the family and 100 healthy controls.

CONCLUSIONA missense mutation c.917G>C in the OTC gene is responsible for the pathogenesis of the disease. Identification of the mutation can facilitate prenatal diagnosis and genetic counseling for the family.

Computational Biology ; Female ; Humans ; Male ; Mutation ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; diagnosis ; genetics ; Sequence Analysis, DNA

OBJECTIVETo analyze the clinical and genetic characteristics of three children with ornithine carbamoyltransferase deficiency(OTCD), and to provide a practical method for gene diagnosis and genetic counseling of the disease.

METHODSAll exons of the ornithine carbamoyltransferase (OTC) gene were screened by polymerase chain reaction-DNA direct sequencing in the three OTCD patients.

RESULTSOne patient firstly presented as vomiting at 6 month of age. A missense mutation of T262I was detected. His mother had the same mutation without any clinical symptoms. The second patient presented as restlessness, and had a missense mutation of R277W. Gene analysis of his parents was not available. The third patient presented as neonatal lethargy, harbored a missense mutation of I172M. His mother had the same mutation without any clinical symptoms.

CONCLUSIONGene mutation analysis is a feasible way for diagnosing OTCD. Patients with I172M mutation present symptom early, while those with T262I and R277W mutations manifest symptoms later. Gene mutation analysis will be important for asymptomatic and prenatal diagnosis and genetic counseling.

Base Sequence ; Child ; Exons ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; genetics ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; genetics ; pathology

Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as >1700 microg/dL (range, 0 to 45 microg/dL). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.
Ammonia ; Hemodiafiltration ; Humans ; Hyperammonemia ; Infant ; Infant, Newborn ; Lethargy ; Metabolism, Inborn Errors ; Ornithine ; Ornithine Carbamoyltransferase ; Ornithine Carbamoyltransferase Deficiency Disease ; Renal Replacement Therapy ; Seizures ; Urea

OTC deficiency is an X-linked disorder in which the synthesis of urea is impaired. OTC catalyzes the synthesis of citrulline from carbamyl phosphate and ornithine. Complete or partial deficiencies of this enzyme may lead to Reye syndrome like picture such as encephalopathy, hepatic dysfunction, hyperammonemia, etc. We recently had a case that was presented as recurrent Reye syndrome, and was effectively treated with hemodialysis, arginine, sodium benzoate, etc. This report describes an experience in treating this condition with review of available literature.
Arginine ; Carbamyl Phosphate ; Citrulline ; Hepatic Encephalopathy ; Hyperammonemia ; Ornithine Carbamoyltransferase Deficiency Disease ; Ornithine Carbamoyltransferase* ; Ornithine* ; Renal Dialysis ; Reye Syndrome ; Sodium Benzoate ; Urea

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.
Humans ; Infant, Newborn ; Male ; Citrulline ; Electroencephalography ; Hyperammonemia ; Ornithine Carbamoyltransferase Deficiency Disease/therapy* ; Seizures

OBJECTIVE: To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD). METHODS: Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted. RESULTS: The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers. CONCLUSION The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.
Child ; Humans ; Ornithine Carbamoyltransferase Deficiency Disease/genetics* ; Exons ; Seizures ; Computational Biology ; Heterozygote

Humans ; Urea Cycle Disorders, Inborn/diagnosis* ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; China

Ornithine transcarbamylase deficiency(OTCD)is a most common ornithine cycle (urea cycle) disorder. It is a X-link inherited disorder caused by
Humans ; Hyperammonemia/etiology* ; Liver Transplantation ; Nervous System Diseases/prevention & control* ; Ornithine Carbamoyltransferase Deficiency Disease/therapy*

OBJECTIVE: To evaluate the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy for patients with Ornithine transcarbamylase deficiency (OTCD). METHODS: Two children with OTCD were selected as the study subjects, and their clinical manifestations, blood ammonia, liver enzymes, growth and development information following the treatment with GPB were retrospectively analyzed. A literature review was also carried out by searching the PubMed database for studies on the GPB treatment for urea cycle disorders. RESULTS: With the GPB treatment, the blood ammonia and liver enzyme level in both patients have decreased to the normal range within 3 months. Motor development in child 2 has improved. No adverse reaction was noted, except for transient palmar greasy smell and loss of appetite in child 1. Analysis of the literature showed that patients had lower ammonia exposure, lower annual incidence of hyperammonemic crisis, more actual protein intake and fewer adverse events during GPB treatment. CONCLUSION GPB is safe and effective for the treatment of OTCD.
Child ; Humans ; Ornithine Carbamoyltransferase Deficiency Disease/drug therapy* ; Phenylbutyrates/therapeutic use* ; Ammonia ; Retrospective Studies