Guidelines for the investigation and management of a reduced level of consciousness in children: implication for clinical biochemistry laboratories

Table 1 of the article by Bowker et al. in the November 2007 issue of the Annals might be misleading (Ann Clin Biochem 2007;44:506–11). Although the data are correct, the notation for ammonia concentration is intuitively reversed (i.e. +++ indicates a low ammonia and + indicates a high ammonia). The table is reproduced below using the correct notation. The Annals apologizes for any misunderstanding that may have been caused.

Table 1

Causes of pathologically raised plasma ammonia

Causes of hyperammonaemia	Relative ammonia concentration	Initial investigations	Confirmatory test
Inherited metabolic disorders
Defects of the urea cycle
N-acetylglutamate synthetase deficiency	+++	Urine orotic acid; plasma and urinary aminoacids and urinary organic acids	Enzyme assay in liver or skin biopsy tissue depending upon the disorder; DNA analysis in some cases
Carbamyl phosphate synthetase deficiency	+++
Ornithine transcarbamylase deficiency	+++
Arginosuccinate synthetase deficiency	+++
Arginosuccinate lyase deficiency	+++
Arginase deficiency	++
Organic acidurias
Propionic acidaemia	+++	Urinary organic acids and amino acids; blood acyl carnitine profile	Enzyme assay; DNA analysis in some cases
Methylmalonic acidaemia	++
Isovaleric acidaemia	+
3-Hydroxy-3-methylglutaryl CoA lyase deficiency	++
Multiple carboxylase deficiency	+
Disorders of fatty acid oxidation
Multiple acyl CoA dehydrogenase deficiency	+++	Plasma free carnitine and acylcarnitine profile; urinary organic and amino acids	Skin fibroblast flux assays; specific enzyme assay. DNA analysis in some cases
Very long chain acyl CoA dehydrogenase deficiency	++
Long chain hydroxyacyl CoA dehydrogenase deficiency	++
Medium chain acyl CoA dehydrogenase deficiency	+
Carnitine acyl carnitine translocase deficiency	++
Carnitine transporter deficiency	+
Carnitine palmitoyl transferase 1 deficiency	++
Other inherited metabolic disorders
Hyperammonaemia, hyperornithinaemia, homocitrullinaemia syndrome	+++	Urinary orotate. Urinary organic and amino acids; intermediary metabolites including lactate, free fatty acids and 3-hydroxybutyrate	Insulin measurement Muscle enzyme and DNA studies in mitochondrial disorders. Enzyme assay in some cases
Lysinuric protein intolerance	+++
Hyperinsulinism hyperammonaemia syndrome	++
Mitochondrial respiratory chain defects	+/++
Pyruvate dehydrogenase deficiency	+++
Acquired hyperammonaemia
Illness/sepsis
Urinary tract infection with a urease producing organism	++	Clinical assessment	Microbiology results and lack of other metabolic diagnoses
Ribavarin therapy	+
5-fluorouracil toxicity	+
Portosystemic shunting	+
Haemorrhage in the GI tract	+
Renal tubular acidosis type 1	+
Reye's Syndrome
	+++	Blood glucose and liver enzyme assay	Abnormal liver biopsy and lack of other metabolic diagnoses
Drugs
Valproate sodium	+++	Drug/therapy clinical history	Absence of other metabolic causes
Chemotherapy	+
Parenteral nutrition	+
Ethanol with starvation	+

+++, blood ammonia ∼600–2000 μmol/L; ++, blood ammonia ∼200–600 μmol/L; +, blood ammonia <200 μmol/L