Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period, and discuss the long-term developmental outcome of survivors. The families of 32 infants, among 43 identified prenatally as being at risk for a urea cycle disorder, chose to have their infants treated according to a diagnostic and therapeutic protocol, beginning at birth. The therapy was effective in avoiding neonatal hyperammonemic coma and death in seven patients with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency. When treated prospectively, five of eight patients with ornithine transcarbamylase deficiency avoided severe hyperammonemia and survived the neonatal period. Two patients with carbamoyl phosphate synthetase deficiency and two with ornithine transcarbamylase deficiency have subsequently died; three additional patients with the latter disorder have received orthotopic liver transplants. Our experience suggests that these surviving patients have had a more favorable neurologic outcome than patients rescued from neonatal hyperammonemic coma. However, all of them require a burdensome medical regimen and may have handicaps that include impairment of development and recurrent episodes of hyperammonemia. Further, those with deficiency of carbamoyl phosphate synthetase or ornithine transcarbamylase have a high mortality rate.
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PMID:Prospective treatment of urea cycle disorders. 172 Apr 58

We describe a male infant with congenital hyperammonaemia due to partial carbamylphosphate synthetase-I (CPS-I) deficiency. At 21 days of age, he had convulsions and at 53 days of age hyperammonaemic coma. Therapy with sodium benzoate, L-arginine, essential amino acids, L-carnitine and peritoneal dialysis lowered the blood ammonia levels, and his clinical manifestations improved. The CPS-I activity in liver tissue obtained by open biopsy was about 25.6% of normal values. The serum and urine free carnitine levels in the patient decreased during the hyperammonaemic crisis and were low at 7 months of age. After oral administration of L-carnitine (10 mg/kg per day) at 7 months of age, the mean blood ammonia levels decreased significantly, accompanied by an increase in serum and urine free carnitine levels. We propose the use of L-carnitine therapy to prevent secondary carnitine deficiency in patients with CPS-I deficiency as well as ornithine transcarbamylase (OTC) deficiency.
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PMID:A case of carbamylphosphate synthetase-I deficiency associated with secondary carnitine deficiency--L-carnitine treatment of CPS-I deficiency. 230 75

A lethal carbamylphosphate synthetase (CPS: EC 6.3.4.16) deficiency (McKusick 23730) was found in a newborn girl; who presented on the second day of life with acute hyperammonaemia, hypotonia, seizures and who died in a coma 6 days after birth. The activity of the mitochondrial urea cycle enzymes, CPS and ornithine transcarbamylase (OTC: EC 2.1.3.3) were measured on a needle biopsy sample taken from liver and showed that CPS was 1.4% of the normal mean (0.09 nmol/min/mg protein) whereas OTC activity was normal (110 nmol/min/mg protein). Immunological analysis of the liver sample showed no detectable immunoreactive CPS and confirmed the presence of normal levels of OTC. RNA was extracted from postmortem liver and in vitro translation experiments showed that there was no translatable CPS mRNA and confirmed that no CPS protein was synthesized in this child. The absence of translatable mRNA is explicable in terms of a genetic defect which results in a failure to synthesize mRNA for CPS, or synthesis of a defective form of mRNA which is not translated.
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PMID:A carbamylphosphate synthetase deficiency with no detectable immunoreactive enzyme and no translatable mRNA. 643 91

Shortly after birth, a newborn girl developed anorexia, hypotonia, apneic attacks and seizures. After 61 h the child died in coma. Biochemically, a highly elevated blood ammonia level was found together with an increased plasma level of the amino acids mainly involved in ammonia detoxication. Enzyme studies in post-mortem liver tissue material revealed a deficiency of carbamoyl-phosphate synthetase (0.9% of the mean value in controls) in combination with an intermediate activity of L-ornithine: 2-oxoglutarate aminotransferase (40% of the mean value in controls).
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PMID:A lethal neonatal variant of carbamoyl-phosphate synthetase deficiency in combination with an intermediate activity of L-ornithine: 2-oxoglutarate amino-transferase. 685 Dec 28

This is a report of a male neonate with hyperammonemia who showed progressive neurologic symptoms and pulmonary bleeding due to carbamyl phosphate synthetase deficiency. This newborn male died in coma after only 119 hours. His elder brothers died under similar circumstances in the first days of life, and a CPS-deficiency is not to be excluded. The pulmonary bleeding in the patient and in one brother caused by hyperammonemia is emphasized. In the pedigree repeated consanguinity could be detected.
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PMID:[Lethal neonatal deficiency of carbamyl phosphate synthetase (author's transl)]. 709 89

This is the first case of fulminant neonatal-onset carbamoyl-phosphate synthase I deficiency treated by continuous hemodiafiltration indicating that this is an available and effective procedure for neonates with hyperammonemic coma.
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PMID:A case of neonatal-onset carbamoyl-phosphate synthase I deficiency treated by continuous haemodiafiltration. 1096 46

Carbamoyl phosphate synthetase I deficiency (CPSID) is a rare metabolic disorder affecting the first enzymatic step of urea cycle. We report clinical manifestations of a female case of late-onset CPSID in Japan. An 18-year-old girl was admitted to emergency room due to acute comatose state. Her parents had no apparent consanguineous history. She had suffered from intermittent psychotic episodes (excitation, aggressive behavior and insomnia) with nausea and vomiting from the age of 13, mostly coinciding with menstrual period. She had minor learning disability without major neurological deficits and convulsions. Her mental status was estimated as normal in her intermenstrual period. She had been diagnosed as having hysteria and premenstrual syndrome. Her neurological findings on admission showed deep coma and hypotonic tetraparesis. Plasma ammonia level was markedly elevated (684 micrograms/dl) without significant liver dysfunction. Blood urea nitrogen decreased to 6 mg/dl. Continuous venovenous filtration with subsequential administration of sodium benzoate and l-arginine was started to eliminate blood ammonia. Although the plasma ammonia level decreased to 300 mu/dl in next 10 hours, severe cerebral edema was observed in head computed tomography subsequently, followed by marked cerebral atrophy. Finally, her consciousness status became almost alert a month after the onset, but her mental status was severely retarded. CPSI activity of her biopsied liver markedly decreased and she was diagnosed as having CPS ID. CPSI cDNA analysis of her biopsied liver demonstrated a V1149G mutation. Genomic DNA analysis showed that she was heterozygous in V1149G mutation. The mutation allele was derived from her father. The causative factor for absence or very low level of maternal CPSI mRNA will require further analysis.
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PMID:[A case of late-onset carbamoyl phosphate synthetase I deficiency, presenting periodic psychotic episodes coinciding with menstrual periods]. 1208 Jun 9

Evaluation of long-term outcome of patients with urea cycle diseases (UCD) is needed for medical decisions and counselling. Own data comparing outcome of UCD patients with the old treatment limited to protein restriction (i.e. close to the natural history) with that of patients on the modern conservative treatment have shown that gains in survival occur at the cost of more mentally retarded surviving patients. We discuss the possible bias in long-term outcome studies of those rare inheritable disorders where non-predictable environmental factors leading to catabolic crises have a crucial impact on prognosis. A combination of peak or initial ammonia value combined with the duration of coma is discussed as a criterion for prognosis of handicap. The neglect of dietary compensation of branched chain amino acid deficiency worsened by phenylbutyrate treatment in some published protocols could well be an additional cause of the non satisfactory long-term results of conservative treatment which--in our view--mainly aim at bridging optimally the period of late neonatal presentation until liver transplantation in patients with CPS and OTC deficiency (except for mild forms).
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PMID:Long-term outcome of urea cycle disorders. 1643 5