Table 3

Metabolic investigations according to patterns of presentation

Presentation	Condition	Specific investigations
Encephalopathy		Urea cycle defects	Urine amino acids
		Organic acidaemias and MSUD	Urine organic acids
			Plasma amino acids
			Blood carnitine and acylcarnitine profile
			Skin biopsy for enzyme analysis
		Fatty acid oxidation defects	As above, plus:
			Blood DNA mutation analysis
		Primary lactic acidoses (e.g. pyruvate dehydrogenase	CSF lactate
		deficiency, pyruvate carboxylase deficiency and	Mitochondrial DNA—blood and muscle
		respiratory chain defects)	Muscle biopsy—histology and electron microscopy
			Skin biopsy—enzymes of pyruvate metabolism
		Non-ketotic hyperglycinaemia	Plasma and CSF amino acids
			Enzyme analysis on transformed lymphoblasts
		Molybdenum cofactor deficiency	Urine sulphite (dipstick)
			Urine amino acids
			Plasma uric acid
			Skin biopsy for enzyme analysis
		Pyridoxine dependent seizures	Trial of pyridoxine under EEG observation
Hypoglycaemia	Fatty acid oxidation defects	As under encephalopathy
	Hypopituitarism	Hormone levels (growth hormone, cortisol, ACTH, insulin, and C peptide)
	Adrenal dysfunction
	Hyperinsulinism
		Gluconeogenic defects (e.g. fructose-1,6 bisphosphatase deficiency)		Blood gases (metabolic acidosis)
				Plasma lactate
				Urine organic acids (for glycerol)
				Enzyme assay—leucocytes or liver biopsy
		Glycogen storage disease (types I, III, VI, IX)		Plasma lactate
				Enzyme assay—leucocytes or liver biopsy
				Histology on liver biopsy
		Secondary to organic acidaemias or disorders affecting the liver	As stated under respective sections
Liver disease		Galactosaemia		Beutler test
				Red cell galactose-1-phosphate
				DNA mutation analysis
				Ophthalmology assessment for cataracts
		Tyrosinaemia type I		Plasma amino acids
				Urine organic acids
				Investigations for renal Fanconi's syndrome
		α₁ Antitrypsin deficiency		Serum α₁ antitrypsin
		α₁ Antitrypsin deficiency		Protease typing
		Neonatal haemochromatosis		Serum ferritin
		Neonatal haemochromatosis		Liver biopsy
		Niemann–Pick C		Foam cells on bone marrow aspitrate, blood film, liver biopsy
		Niemann–Pick C		Filipin staining on skin biopsy
		Mitochondrial (respiratory chain) defects		CSF lactate
				Mitochondrial DNA—blood and muscle
				Muscle and liver biopsy—histology and electron microscopy
Cardiomyopathy		Pompe's disease (GSD type II)	Enzyme assay on lymphocytes or skin fibroblasts
		Fatty acid oxidation defects	As stated under encephalopathy
		Mitochondrial (respiratory chain) defects	As stated under liver disease
		CDG 1a syndrome		Serum transferrin isoelectric focusing
		CDG 1a syndrome		Enzyme assay on skin biopsy
		Lysosomal storage disorders		White cell enzymes
				Urine oligosaccharides and mucolpolysaccharides
				Skin biopsy
Dysmorphism		Lysosomal storage disorders	As under cardiomyopathy
		Disorders of sterol synthesis		Urine organic acids
				Plasma 7-dehydrocholesterol
				Skin biopsy
		CDG syndrome		Serum transferrin isoelectric focusing
		CDG syndrome		Enzyme assay on skin biopsy
		Glutaric aciduria type II		Urine organic acids
				Blood carnitine/acylcarnitine profile
				Skin biopsy