organic acids, neurotransmitters, folate, pterins, other disease-specific metabolites Mitochondrial disorders Nonketotic hyperglycinemia Neurotransmitter disorders a Within disease categories, not all diseases have the laboratory abnormality In disorders of protein metabolism, carbohydrate metabolism, and fatty acid oxidation defects and abnormality may be present only during acute crisis b Samples, quantities required, collection method, preparation, and storage are institution dependent Tandem mass spectrometry measures amino acids and acylcarnitines, derived from carnitine, which combines with acyl-CoA derived from fatty acids and organic acids (which may have been derived from amino acids) Tandem mass spectrometry may be used as a screen for aminoacidopathies, organic acidemias, and fatty acid oxidation defects Confirmation of diagnosis usually requires further testing, including plasma amino acids, urinary organic acids, histologic examination, DNA analysis, and enzyme and/or biochemical assays c Total minimum is mL for organic acids and acylglycines EDTA, ethylenediaminetetraacetic acid; GI, gastrointestinal; IEM, inborn error of metabolism Hyperammonemia Ammonia is an intermediary in the catabolism of nitrogen-containing compounds, particularly amino acids Normal ammonia levels are less than 100 μg/dL in neonates and less than 80 μg/dL beyond the neonatal period Elevated ammonia is neurotoxic and immediate treatment should begin pending confirmation of a specific diagnosis Early manifestations of hyperammonemia are anorexia and irritability, followed by rapid progression to vomiting, lethargy, seizures, coma, and death in hours Marked hyperammonemia causes brainstem dysfunction leading to deep rapid breathing and resulting in respiratory alkalosis, a hallmark of urea cycle disorders Cerebral edema and intracranial hemorrhage are also common Children and adolescents may report headache, abdominal pain, and fatigue Some patients with chronic hyperammonemia adapt to their elevated ammonia level and may appear to have no overt symptoms despite elevated ammonia