Acute pediatric hyperammonemia: current diagnosis and management strategies

Abstract

Acute hyperammonemia may induce a neurologic impairment leading to an acute life-threatening condition. Coma duration, ammonia peak level, and hyperammonemia duration are the main risk factors of hyperammonemia-related neurologic deficits and death. In children, hyperammonemia is mainly caused by severe liver failure and inborn errors of metabolism. In an acute setting, obtaining reliable plasma ammonia levels can be challenging because of the preanalytical difficulties that need to be addressed carefully. The management of hyperammonemia includes 1) identification of precipitating factors and cerebral edema presence, 2) a decrease in ammonia production by reducing protein intake and reversing catabolism, and 3) ammonia removal with pharmacologic treatment and, in the most severe cases, with extracorporeal therapies. In case of severe coma, transcranial Doppler ultrasound could be the method of choice to noninvasively monitor cerebral blood flow and titrate therapies.

Keywords: critical care; hemodialysis; hyperammonemia; pediatrics; sodium benzoate; sodium phenylacetate.

Figure 1

Putative mechanisms underlying hyperammonemia encephalopathy and brain edema.

Figure 2

Diagnostic algorithm facing hyperammonemia Note: Adapted from Haberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32. Abbreviations: AR1D, arginase 1 deficiency; ASLD, arginosuccinate lyase deficiency; ASSD, arginosuccinate synthetase deficiency; CPS1-D, carbamoylphosphate synthetase 1 deficiency; NAGS-D, N-acetylglutamate synthetase deficiency; OTCD, ornithine transcarbamylase deficiency.

Figure 3

Urea cycle and therapies for hyperammonemia. Notes: Each number corresponds to a urea cycle deficiency disease: 1 = N-acetylglutamate synthase; 2 = carbamoylphosphate synthetase 1; 3 = ornithine transcarbamylase; 4 = arginosuccinate synthetase; 5 = arginosuccinate lyase; 6 = arginase deficiency. Abbreviation: CoA, coenzyme A.

Figure 4

Suggested algorithm for management of hyperammonemia symptomatic patients according to Guideline Development Group – Grade of recommendation C–D. Source: Adapted from Haberle J, Boddaert N, Burlina A, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32. Abbreviations: CPS1D, carbamoylphosphate synthetase 1 deficiency; IV, intravenous; NAGSD, N-acetylglutamate synthetase deficiency; OTCD, ornithine transcarbamylase deficiency; TCD, transcranial Doppler; UCD, urea cycle defect.