sodium-benzoate and Carbamoyl-Phosphate-Synthase-I-Deficiency-Disease

The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects.. We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia.. Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, P<0.001). Patients 12 or more years of age (93 patients), who had 437 episodes, were more likely than all younger patients to survive (99%, P<0.001). Eighty-one percent of patients who were comatose at admission survived. Patients less than 30 days of age with a peak ammonium level above 1000 micromol per liter (1804 microg per deciliter) were least likely to survive a hyperammonemic episode (38%, P<0.001). Dialysis was also used in 56 neonates during 60% of episodes and in 80 patients 30 days of age or older during 7% of episodes.. Prompt recognition of a urea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate.

Topics: Adolescent; Adult; Age Factors; Age of Onset; Amino Acid Metabolism, Inborn Errors; Ammonia; Carbamoyl-Phosphate Synthase I Deficiency Disease; Child; Child, Preschool; Citrullinemia; Female; Humans; Hyperammonemia; Infant; Infant, Newborn; Male; Ornithine Carbamoyltransferase Deficiency Disease; Phenylacetates; Sodium Benzoate; Survival Analysis; Urea

Long-term survival of patients with neonatal-onset carbamoyl-phosphate synthetase 1 deficiency (CPS1D), an autosomal recessive disorder characterized by repeated, life-threatening hyperammonemia, is rare. We describe the diagnosis and clinical management of a teenager with neonatal-onset CPS1D who did not undergo therapeutic liver transplantation.. Following emergent neonatal therapy, the patient was diagnosed with CPS1D based on clinical, radiological, biochemical and genetic analyses. Her clinical course, neurobehavioral development and therapeutic interventions are presented and discussed.. Born from nonconsanguineous parents, the proband underwent phototherapy for neonatal jaundice, associated with acute encephalopathy, apnea and cerebral edema. Based on blood and urinary biochemical abnormalities, neonatal-onset CPS1D was diagnosed. Her hyperammonemia was corrected by hemodialysis, followed by sodium benzoate, L-arginine, levocarnitine and protein-free diet therapy. Because of a relapse and persistent neurobehavioral regression by age 1, a planned liver transplantation was cancelled. At age 10, sodium phenylbutyrate was substituted as ammonia scavenger. Genetic testing revealed compound heterozygote c.2359C>T (R787X) and c.236+6T>C variants of CPS1, confirming her diagnosis. Despite severe neurological sequelae, the patient is 16 and in stable condition.. Our case suggests that early hemodialysis and pharmacologic interventions for acute neonatal hyperammonemia can improve the prognosis of patients with neonatal-onset CPS1D.

Topics: Arginine; Brain Diseases, Metabolic; Carbamoyl-Phosphate Synthase I Deficiency Disease; Carnitine; Female; Humans; Hyperammonemia; Infant, Newborn; Phenylbutyrates; Renal Dialysis; Sodium Benzoate