Citrullinemia type I is an urea cycle defect caused by mutations in the argininosuccinate synthetase (ASS1) gene. We report a novel argininosuccinate synthetase gene mutation in a Korean family with type I citrullinemia. Metabolic evaluation revealed significant hyperammonemia. Amino acid/acylcarnitine screening using tandem mass spectrometry showed high level of citrulline. Plasma amino acid analysis showed high level of citrulline and the urine organic acid analysis showed makedly increased level of orotic acid. To confirm diagnosis of citrullinemia we did mutation analysis of the ASS1 gene. The patient was found to have mutations of c.689G>C (p.G230A) and c.892G>A (p.E298K), which were new types of argininosuccinate synthetase gene mutation have never been reported in Korea. We report a novel case of argininosuccinate synthetase 1 gene mutation and suggest that the gene study to the family members is necessary to carry out when a patient is diagnosed as citrullinemia.
Argininosuccinate Synthase ; Citrulline ; Citrullinemia ; Humans ; Hyperammonemia ; Korea ; Mass Screening ; Orotic Acid ; Plasma ; Tandem Mass Spectrometry ; Urea

Citrullinemia type I is an urea cycle defect caused by mutations in the argininosuccinate synthetase (ASS1) gene. We report a novel argininosuccinate synthetase gene mutation in a Korean family with type I citrullinemia. Metabolic evaluation revealed significant hyperammonemia. Amino acid/acylcarnitine screening using tandem mass spectrometry showed high level of citrulline. Plasma amino acid analysis showed high level of citrulline and the urine organic acid analysis showed makedly increased level of orotic acid. To confirm diagnosis of citrullinemia we did mutation analysis of the ASS1 gene. The patient was found to have mutations of c.689G>C (p.G230A) and c.892G>A (p.E298K), which were new types of argininosuccinate synthetase gene mutation have never been reported in Korea. We report a novel case of argininosuccinate synthetase 1 gene mutation and suggest that the gene study to the family members is necessary to carry out when a patient is diagnosed as citrullinemia.
Argininosuccinate Synthase ; Citrulline ; Citrullinemia ; Humans ; Hyperammonemia ; Korea ; Mass Screening ; Orotic Acid ; Plasma ; Tandem Mass Spectrometry ; Urea

OBJECTIVEThis study aimed at understanding clinical features, biochemistry and gene mutation in one Chinese pedigree which had a neonatal-onset ornithine transcarbamylase deficiency (OTCD) boy, and exploring the significance of ornithine transcarbamylase analysis in prenatal diagnosis.

METHODThe clinical and biochemical data of one case were analyzed. The amino acids in blood and organic acids in urine were analyzed by mass spectrum technology. The OTC gene mutation was detected using polymerase chain reaction (PCR) and DNA direct sequencing for the case, his parents and the fetus amniocyte and her blood after birth.

RESULTThe age of onset was 3 days after birth, he began to have poor reaction, difficulty to feed, high blood ammonia, infection, slight metabolic acidosis, which were consistent with the clinical diagnosis of urea cycle disorders. The boy died at the age of 9 days. Citrulline of blood was detected twice, and were 0.86 µm and 1.06 µm, respectively. The orotic acid was elevated (124 µm/M Creatinine), and urine lactic acid was significantly elevated. The citrulline and orotic acid in his parents and their second baby were normal in DBS and urine. One nonsense mutation in the OTC gene was found at the exon 9 (C. 958 C > T) and his mother was the heterozygote, which caused an arginine to terminate the code at position 320 of the protein (R320X). Two other mutations were also detected at intron 9 (C.1005 + 132 InsT) and intron 5 (C.542 + 134 G > G/A). But the analysis of his father's DNA, the fetus amniocyte and her blood was normal.

CONCLUSIONThe mutation of C. 958 C > T in OTC gene may occur during neonatal period. This mutation would result in a very severe symptom, even die suddenly several days after birth, if it was a boy. It needs more researches to discuss whether the C.1005 + 132 InsT in intron 9 and C.542 + 134 G > G/A in intron 5 were associated with the neonatal-onset OTCD. The DNA analysis of OTC gene could be utilized for the prenatal diagnosis.

Citrulline ; analysis ; DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; genetics ; physiopathology ; Orotic Acid ; analysis ; Pedigree

CT and MR appearance of the brain in three children with ornithine transcarbamylase (OTC) deficiency are described. They showed clinical signs of vomiting and convulsion and were diagnosed by measurement of plasma ammonium, amino acids, acid-base balance, and urinary orotic acid levels. CT and MR were performed within one month from the onset of the symptom. CT and MRI demonstrated brain swelling with small ventricles and diffuse low density of white matter, which indicated cerebral hypoperfusion secondary to elevated intracranial pressure. With more prolonged survival hyperammonemia may cause cerebral atrophy. CT and MR appearance in these cases resembled a hypoxic brain damage and this finding should be included in the differential diagnosis.
Acid-Base Equilibrium ; Amino Acids ; Ammonium Compounds ; Atrophy ; Brain ; Brain Edema ; Child ; Diagnosis, Differential ; Humans ; Hyperammonemia* ; Hypoxia, Brain ; Intracranial Hypertension ; Magnetic Resonance Imaging* ; Ornithine Carbamoyltransferase Deficiency Disease* ; Ornithine Carbamoyltransferase* ; Ornithine* ; Orotic Acid ; Plasma ; Seizures ; Vomiting

Purine & pyrimidine nucleotides are basic constituents of cellular DNA and RNA polynucleotides. Their function includes regulation of cell metabolism and function, energy conservation and transport and formation of coenzymes and active intermediates of phospholipids and carbohydrate metabolism. The origin of cellular purines and pyrimidines is almost exclusively endogenous source, and the dietary purines play only a minor role. Diagnostic and clinical markers of purine and pyrimidine nucleotide disorders are the level of uric acid, xanthine, hypoxanthine, orotic acid, uracil, thymine, dihydrouracil, dihydrothymine, and succinyladenosine. Clinical manifestations of purine and pyrimidine metabolic disorders are crystalluria and acute renal failure, infections, failure to thrive, and anemia. One of purine metabolic disorders, Lesch-Nyhan disease, is X-linked recessive disorder, presenting motor delay, cerebral palsy, involuntary movements, self-injurious behavior, hyperurcemia, uricosuria, urinary calculi and gouty arthritis. Hypoxanthine-guanine phosphoribosyl transferase(HPRT) is deficient.
Acute Kidney Injury ; Anemia ; Arthritis, Gouty ; Carbohydrate Metabolism ; Cerebral Palsy ; Coenzymes ; DNA ; Dyskinesias ; Failure to Thrive ; Hypoxanthine ; Lesch-Nyhan Syndrome* ; Metabolism* ; Orotic Acid ; Phospholipids ; Polynucleotides ; Purines ; Pyrimidine Nucleotides ; Pyrimidines ; RNA ; Self-Injurious Behavior ; Thymine ; Uracil ; Uric Acid ; Urinary Calculi ; Xanthine ; Biomarkers