Hyperammonemia in Inherited Metabolic Diseases

Case report: Is exchange transfusion a possible treatment for metabolic decompensation in neonates with methylmalonic aciduria in the setting of limited resources?

“…Hyperammonemia is a severe complication of MMA, with high mortality and permanent neurological sequelae in survivors, which may be caused by the inhibition effects of the accumulation of organic acids in the urea and tricarboxylic acid cycles ( 2 , 3 ). In patients with MMA, the abnormal accumulation of propionyl-CoA inhibits the urea cycle by reducing the synthesis of N-acetylglutamate, an essential activator of carbamylphosphate synthetase ( 5 ).…”

“…As a result, the ammonia produced by protein degradation cannot be detoxified in the liver by binding it to the urea cycle, resulting in high ammonia concentration in the blood ( 6 ). Moreover, the synthesis of succinyl-CoA in MMA is impaired, which facilitates the degradation of glutamine to produce α-ketoglutarate to improve the activity of the Krebs cycle activity, which contributed to chronic hyperammonemia ( 2 ). There are also some scholars who believe that because the low level of carnitine is related to the suppressed expression of urea cycle enzymes, secondary carnitine deficiency in MMA may lead to hyperammonemia ( 2 , 7 , 8 ).…”

“…It does not only compensate for secondary carnitine deficiency due to the loss of carnitine combined with organic acids in urine but also has antioxidant and anti-inflammatory effects, which may improve or prevent neurological damages caused by excessive ammonia ( 1 , 11 , 12 ). Besides, disaccharide lactulose, sodium benzoate, N-acetylglutamate analog, and so on are also used in the management of hyperammonemia ( 1 , 2 ). Extracorporeal detoxification should be considered and prepared to start in neonates with a serum ammonia level above 400–500 μmol/l, or the neonates who do not respond to medical treatment within 4 to 6 h ( 1 , 13 ).…”

“…It is characterized by the abnormal accumulation of branched-chain amino acid metabolites, such as methylmalonic acid, malonic acid, 3-hydroxy propionic acid, and methyl citrate ( 1 ). Hyperammonemia is a neonatal emergency, with high mortality, and permanent neurological sequelae for survivors ( 2 , 3 ). As a result, timely and effective treatment of this disease is crucial to reducing mortality and morbidity.…”

Diagnosis and Management of Inborn Errors of Metabolism in Adult Patients in the Emergency Department

“…Hyperammonemia is a potentially life-threatening complication mainly observed in the congenital defects of the urea cycle, classical organic acidurias and the defects of mitochondrial fatty acid oxidation. Duration and severity of hyperammonemia strongly correlates with brain damage, so effective and prompt diagnosis and treatment is crucial to prevent irreversible neurological damage [24].…”