Detection of CPS1 gene mutation in a neonate with carbamoyl phosphate synthetase I deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a neonate featuring hyperammonemia.@*METHODS@#The patient was examined and tested by tandem mass spectrometry and next generation sequencing (NGS). Suspected mutations were confirmed by Sanger sequencing of the proband and her parents. Potential impact of the mutation was predicted with SIFT, PolyPhen-2 and MutationTaste software.@*RESULTS@#Plasma ammonia and alanine were significantly increased in the proband, while serum citrulline was decreased. The neonate was found to harbor compound heterozygous mutations of the CPS1 gene [c.1631C>T(p.T544M) and c.1981G>T(p.G661C)], which were respectively inherited from her father and mother.@*CONCLUSION@#The carbamoyl phosphate synthetase I deficiency of the proband can probably be attributed to the mutations of the CPS1 gene. Above finding has expanded the spectrum of CPS1 mutations in association with carbamoyl phosphate synthetase I deficiency.

Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.

The relationship of CPS-I, OCT and hepatic encephalopathy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the role of carbamyl phosphate I (CPS-I)and ornithine transcarbamoylase (OCT) levels in cirrhosis patients with and without hepatic encephalopathy, and to analyze the correlations between CPS-Iand OCT with the development of hepatic encephalopathy.</p><p><b>METHODS</b>CPS-I, OCT, plasma ammonia and liver function of 95 cirrhosis patients with hepatic encephalopathy and 25 cirrhosis patients without hepatic encephalopathy in our hospital from January 2008 to December 2009 were analyzed. 60 healthy controls were recruited in the control group. The differences of serum CPS-I, OCT levels among the cirrhosis patients with and without hepatic encephalopathy and the healthy controls were analyzed; the correlations of CPS-I, OCT levels with plasma ammonia and total protein in cirrhosis patients,and the correlations of CPS-I, OCT levels with Child-Pugh classification of cirrhosis symptom severity in cirrhosis were analyzed. the clinical characteristics between patients who had HE and no HE with chi-square tests were compared. Comparisons of CPS-I, OCT levels across patients based on the Child-Pugh classification were performed with One-Way ANOVA and Student-Newman-Keuls, correlation of CPS-I, OCT with other indicators were performed with Pearson correlation analysis.</p><p><b>RESULTS</b>Serum CPS-I and OCT levels in cirrhosis patients with hepatic encephalopathy were (143.3+/-48.5) U/L, (297.0+/-102.6) is multiplied by 10 U/L, which were lower than that in cirrhosis patients without hepatic encephalopathy (180.3+/-51.5) U/L, (351.8+/-109.0) is multiplied by 10 U/L (t = 2.53, t = 2.78, P < 0.01). Compared with healthy controls, serum CPS-I and OCT levels in cirrhosis patients with and without hepatic encephalopathy were all lower (t = 3.21, t = 4.16, t = 2.12, t = 3.15, P < 0.05). CPS-I was correlated with OCT, (r = 0.946, P < 0.05); CPS-I and OCT were negatively correlated with ALT and AST (r = -0.284, r = -0.239, r = -0.303, r = -0.322, P < 0.05). Additionally, CPS-I and OCT levels were negatively correlated with the Child-Pugh classification in Cirrhosis (F = 10.13, F = 20.28, P < 0.01).</p><p><b>CONCLUSION</b>The serum CPS-I and COT levels were important factors affecting plasma ammonia in patients with cirrhosis and played an important role in the development of hepatic encephalopathy.</p>

Citrulinemia / Citrulinemia

Se describen los casos clínicos de tres pacientes con citrulinemia, que fue diagnosticada respectivamente a las edades de tres meses, siete días y siete meses. En todos la concentración sanguínea de amonio era anormalmente alta (>200ug por ciento) y las de citrulina en suero fueron de 353, 1.759, 289 nm/ml respectivamente. El tratamiento consistió en una dieta hipoproteica e hipercalórica, con suplementos de L-carnitina (100 mg x kg x día). L-arginina (70 a 120 mg x kg x día) y vitaminas. Las manifestaciones clínicas de la enfermedad son mas severas y precoces cuanto menor es la actividad residual de la rginina succínico sintetasa, cuya deficiencia es responsable del trastorno y que está practicamente ausente en la forma neonatal

Hiperamoniemia congénita: informe de 1 paciente / Congenital hyperammonemia: report of a patient

Se presenta un paciente que padece de hiperamoniemia congénita por déficit enzimático del ciclo de la urea. Se plantea por las características clinicohumorales que sea debido a un déficit parcial de carbamilfosfato sintetasa. Se hacen comentarios al respecto

Encefalopatía con degeneración grasa de las vísceras: síndrome de Reye / Encephalopathy with fatty degeneation of the viscera: Reye's syndrome

El síndrome de Reye es una encefalopatía con infiltración grasa de las vísceras que se presenta en niños durante o después del curso de una enfermedad viral respiratoria, gastrointestinal o de una varicela. La microscopía electrónica muestra una marcada alteración de la matriz de las mitocondrias. Bioquímicamente hay una marcada elevación del amonio en sangre que se cree sea debida a una disminución de dos enzimas del ciclo de la úrea que están localizadas dentro de la matriz mitocondrial: carbamil fosfato sintetasa y ornitina trascarbamilasa.