Analysis of AGR1 gene variants in an infant with early-onset argininemia / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for an infant with early-onset argininemia.@*METHODS@#Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing.@*RESULTS@#Genetic testing indicated that he has carried c.560+2T>C and c.811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c.560+2T>C was suspected to be pathogenic, while c.811T>C was of unknown clinical significance, and both were not reported previously.@*CONCLUSION@#The c.560+2T>C and c.811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.

Serum lipid profile, liver function indices and electrolyte levels in diabetics and subjects with hepatic impairment in the University of Port Harcourt Teaching Hospital

This study investigated serum lipid profile, liver function indices and electrolyte levels in diabetics and hepatitics in the University of Port Harcourt Teaching Hospital. 210 subjects comprising 70 subjects each for diabetics, hepatitics, and control matched for age and sex were sampled for the purpose of the study based upon specified criteria. 45 each were males while 25 each were females. Mean alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) activities, respectively, were significantly elevated (p<0.05) in the diabetics (22 U/L, 30 U/L, 91 U/L, and 12 U/L respectively) and hepatitics (86 U/L, 161 U/L, 113 U/L, and 50 U/L respectively); mean triglycerides (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) levels respectively, were significantly elevated (p<0.05) in the diabetics (1.8 mmol/L, 4.6 mmol/L, and 2.6 mmol/L respectively) and hepatitics (1.4 mmol/L, 3.6 mmol/L, and 1.8 mmol/L respectively) except the hepatitics mean LDL-C level, whereas mean high density lipoprotein-cholesterol (HDL-C) level was significantly reduced (p≥0.05) in the diabetics (1.2 mmol/L) and hepatitics (1.0 mmol/L). Mean sodium and potassium levels were significantly reduced (p≥0.05) in the diabetics (135 mmol/L and 3.5 mmol/L respectively). Mean sodium level was reduced in the hepatitics while mean potassium level was elevated in the hepatitics. Mean bicarbonate level was significantly elevated (p<0.05) in the diabetics (28 mmol/L) but slightly elevated in the hepatitics. Conclusively, differences in lipids, electrolyte levels and liver function indices found in diabetics and hepatitics have a great potential as a diagnostic means in clinical practice

Seven patients of argininemia with spastic tetraplegia as the first and major symptom and prenatal diagnosis of two fetuses with high risk / 中华儿科杂志

<p><b>OBJECTIVE</b>Argininemia is a rare disorder of urea cycle defect. The clinical manifestations of this disorder are similar to those of cerebral palsy so that the diagnosis is usually much delayed. This study aimed to investigate the phenotypes and genotypes of seven Chinese patients suffering from argininemia.</p><p><b>METHOD</b>Three boys and four girls with spastic tetraplegia were diagnosed as argininemia by blood aminoacids analysis and ARG1 gene study. Patients were given a protein-restricted diet, citrulline, sodium benzoate, and other treatment intervention. The mother of Patient 5 and 6 accepted genetic counseling and underwent prenatal diagnosis by amniocentesis.</p><p><b>RESULT</b>Seven patients presented with progressive spastic tetraplegia and poor physical growth from the age of 1 month to 4 years. Argininemia was found at the age of 1 year and 10 months to 12 years. Five patients had mental retardations. Three had seizures. Their blood arginine elevated (86.66 to 349.83 µmol/L, normal controls 5 to 25 µmol/L). Liver dysfunction was found in six patients. Five patients had elevated blood ammonia levels. In four patients, cerebral atrophy was observed by cranial magnetic resonance imaging. Nine mutations in the ARG1 gene were identified from 7 patients. Only two mutations, c.703G > A in exon 7 and c.32T > C in exon 1 had been reported. c.34G > T, c.53G > A, c.67delG, c.232dupG, c.374C > T, c.539G > C and c.646-649delCTCA, were novel mutations of ARG1. A homozygous mutation c.703G > A was found in the amniocytes of Patient 5's mother, indicating that the fetus was affected by argininemia. Induced abortion was performed. c.53G > A from Patient 6 was not found in the amniocytes of her mother, indicating that the fetus was not affected by hepatocyte arginase deficiency. The result was confirmed by postnatal mutation analysis of cord blood and the normal blood arginine of the newborn.</p><p><b>CONCLUSION</b>Argininemia is one of the few treatable causes of pediatric spastic paralysis. In this study, seven Chinese patients with spastic tetraplegia were detected by blood aminoacids analysis and confirmed by molecular analysis. Seven novel mutations on ARG1 gene were identified. Prenatal diagnosis of the fetus of a family was performed by amniocytes ARG1 gene analysis.</p>

Advances in clinical and molecular genetics studies on argininemia / 中国当代儿科杂志

Argininemia is a rare, autosomal recessive, metabolic disorder caused by an hereditary deficiency of hepatocytes arginase due to ARG1 gene defect. Arginase is the final enzyme in the urea cycle, catalyzing the hydrolysis of arginine to ornithine and urea. Research advances in the clinical manifestations, diagnosis, treatment, prenatal diagnosis and genetics of argininemia were reviewed in this paper. The clinical manifestations of patients with argininemia are complicated and nonspecific so that clinical diagnosis is usually difficult and delayed. Progressive spastic tetraplegia, seizures and cerebella atrophy are common clinical features of the disease. Blood amino acids analysis, arginase assay and ARG1 gene analysis are important to the diagnosis of argininemia. Early diagnosis and a protein-restricted diet with citrulline and benzoate supplements can contribute a lot to improve patient prognosis. With the application of liquid chromatography-tandem mass spectrometry in selective screening and newborn screening for inborn errors of metabolism, an ever-increasing number of patients with argininemia are detected at the asymptomatic or early stages.

Arginase deficiency.

Hyperargininemia due to arginase deficiency is a rare, inherited, urea cycle disorder. We report a case of arginase deficiency in a 5-year old boy presenting with mild hyperammonemia, hyperargininemia, and dibasic aminoaciduria.