sodium-benzoate and Metabolism--Inborn-Errors

Sodium benzoate is widely used in the Alimentary Industry at low doses for its antimicrobial action. It has also been used as a liver function test. The principle is to evaluate the liver capacity for conjugation of glycine to benzoic acid and to form hippuric acid which is excreted in the urine. In hyperammonemic syndromes, secondary to enzymatic deficiency of the urea cicle, sodium benzoate has the property to act as an alternative way of nitrogen excretion to urinary hippurate instead of urea. Recently, it has been proposed as a therapeutic alternative in cirrhotic patients with portal systemic encephalopathy. Historical, biochemical and clinical data which constitute the principles to validate its clinical application in Hepatology are reviewed in this manuscript.

Topics: Acetates; Adult; Animals; Child; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glycine; Hepatic Encephalopathy; Hippurates; Humans; Hyperammonemia; Liver Cirrhosis; Liver Function Tests; Male; Metabolism, Inborn Errors; Mice; Molecular Structure; Rats; Sodium Benzoate; Urea

Topics: Arginine; Creatine; Diet; Female; Glycine; Guanidinoacetate N-Methyltransferase; Humans; Intellectual Disability; Language Development Disorders; Male; Metabolism, Inborn Errors; Movement Disorders; Ornithine; Sodium Benzoate

Deficiency of any of the 5 enzymes in the urea cycle results in the accumulation of ammonia, leading to encephalopathy; which if untreated, can be lethal and produce devastating neurologic sequelae in long-term survivors. We hereby present an interesting case that presented with hyperammonemia and encephalopathy; later found to have an urea cycle defect.

Topics: Diagnosis, Differential; Glucocorticoids; Hepatic Encephalopathy; Humans; Hyperammonemia; Male; Metabolism, Inborn Errors; Middle Aged; Phenylbutyrates; Prednisone; Sodium Benzoate; Urea

Intravenous sodium benzoate and sodium phenylacetate have been used successfully in the treatment of acute hyperammonaemia in patients with urea cycle disorders. They provide alternative pathways for waste nitrogen disposal and help maintain nitrogen homeostasis. However, we report three patients with hyperammonaemia who received inappropriate doses of intravenous sodium benzoate and sodium phenylacetate that resulted in severe complications. Ambiguous medical prescriptions and inadequate cross-checking of drug dosage by physicians, nurses and pharmacists were the main causes of these incidents. All the patients presented with alteration in mental status, Kussmaul respiration and a partially compensated metabolic acidosis with an increased anion gap. Two patients developed cerebral oedema and hypotension and died. The third survived after haemodialysis. Plasma levels of benzoate and phenylacetate were excessively high. The possible mechanisms of toxicity, management and safety measures are discussed.

Topics: Child; Child, Preschool; Drug Overdose; Fatal Outcome; Female; Humans; Injections, Intravenous; Male; Metabolism, Inborn Errors; Ornithine Carbamoyltransferase; Ornithine Carbamoyltransferase Deficiency Disease; Phenylacetates; Quaternary Ammonium Compounds; Sodium Benzoate; Urea

Inborn errors of urea synthesis result in hyperammonemia. Sodium benzoate (SB) therapy has been beneficial in the treatment of hyperammonemia. It conjugates with glycine to form hippurate, which is then excreted. SB has also been used to treat children with nonketotic hyperglycinemia (NKH), where glycine is removed, on conjugation, as hippurate. In mammalian liver mitochondria, SB is activated by an ATP-dependent reaction to its CoA ester, before conjugation with glycine. Pantothenic acid (PA) is the precursor of CoA. In this investigation, increasing the amounts of PA increased CoA levels in HepG2 cells. It also significantly increased formation of hippurate in SB-treated cells. These findings suggest a beneficial effect of PA on the SB therapy in children with NKH as well as hyperammonemia.

Topics: Cell Line; Hippurates; Humans; Metabolism, Inborn Errors; Pantothenic Acid; Sodium Benzoate

Topics: Dextromethorphan; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Female; Food Preservatives; gamma-Aminobutyric Acid; Glycine; Humans; Infant, Newborn; Male; Metabolism, Inborn Errors; Sodium Benzoate; Vigabatrin