Table 3

Metabolic investigations according to patterns of presentation

Presentation Condition Specific investigations
EncephalopathyUrea cycle defectsUrine 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 dehydrogenaseCSF lactate
deficiency, pyruvate carboxylase deficiency andMitochondrial DNA—blood and muscle
respiratory chain defects)Muscle biopsy—histology and electron microscopy
Skin biopsy—enzymes of pyruvate metabolism
Non-ketotic hyperglycinaemiaPlasma and CSF amino acids
Enzyme analysis on transformed lymphoblasts
Molybdenum cofactor deficiencyUrine sulphite (dipstick)
Urine amino acids
Plasma uric acid
Skin biopsy for enzyme analysis
Pyridoxine dependent seizuresTrial of pyridoxine under EEG observation
HypoglycaemiaFatty acid oxidation defectsAs under encephalopathy
HypopituitarismHormone levels (growth hormone, cortisol, ACTH, insulin, and C peptide)
Adrenal dysfunction
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 liverAs stated under respective sections
Liver diseaseGalactosaemiaBeutler test
Red cell galactose-1-phosphate
DNA mutation analysis
Ophthalmology assessment for cataracts
Tyrosinaemia type IPlasma amino acids
Urine organic acids
Investigations for renal Fanconi's syndrome
α1 Antitrypsin deficiencySerum α1 antitrypsin
Protease typing
Neonatal haemochromatosisSerum ferritin
Liver biopsy
Niemann–Pick CFoam cells on bone marrow aspitrate, blood film, liver biopsy
Filipin staining on skin biopsy
Mitochondrial (respiratory chain) defectsCSF lactate
Mitochondrial DNA—blood and muscle
Muscle and liver biopsy—histology and electron microscopy
CardiomyopathyPompe's disease (GSD type II)Enzyme assay on lymphocytes or skin fibroblasts
Fatty acid oxidation defectsAs stated under encephalopathy
Mitochondrial (respiratory chain) defectsAs stated under liver disease
CDG 1a syndromeSerum transferrin isoelectric focusing
Enzyme assay on skin biopsy
Lysosomal storage disordersWhite cell enzymes
Urine oligosaccharides and mucolpolysaccharides
Skin biopsy
DysmorphismLysosomal storage disordersAs under cardiomyopathy
Disorders of sterol synthesisUrine organic acids
Plasma 7-dehydrocholesterol
Skin biopsy
CDG syndromeSerum transferrin isoelectric focusing
Enzyme assay on skin biopsy
Glutaric aciduria type IIUrine organic acids
Blood carnitine/acylcarnitine profile
Skin biopsy