Test creatine kinase if symptoms of myopathy/muscular dystrophy are present.
Lactate and pyruvate may be abnormal in mitochondrial and related disorders.
Quantitative amino acids, total plasma homocysteine, folate, and vitamin B12 levels detect disorders of amino acid metabolism and homocystinuria associated with disorders of vitamin B12 and folate metabolism.
Urine organic acids may detect elevated NAA levels characteristic of Canavan's disease in addition to organic acid disorders associated with leukoencephalopathy, including glutaric aciduria type 1, L-2-hydroxyglutaric aciduria, 3-methylglutaconic aciduria type 1, and biotinidase deficiency.
Very long chain fatty acids, pipecolic acid, phytanic acid, and other peroxisomal studies detect X-linked adrenoleukodystrophy, peroxisomal biogenesis defects, and single peroxisomal enzyme defects.
Urine may be tested for mucopolysaccharides, oligosaccharides, sulfatides (for metachromatic leukodystrophy), and ceramides (for Fabry's disease).
Specific lysosomal enzyme assays detect lysosomal disorders, including metachromatic leukodystrophy and Krabbe's disease.
Specific molecular studies may be initiated based on clinical and MRI characteristics.
Comparative genome hybridization microarray may detect a microdeletion or microduplication, particularly in patients with stable leukoencephalopathy and dysmorphic features.
Lumbar puncture may be needed for evaluation of lactate (mitochondrial disorders), amino acids (serine biosynthesis defects), and disorders associated with cerebral folate deficiency, which may not be detected with routine blood and urine tests.
Skin biopsy for fibroblast culture is useful for enzymatic and DNA based testing for follow-up of initial screening tests. Electron microscopy of skin may reveal inclusions suggestive of a particular underlying disorder.
Muscle biopsy may be needed to investigate for mitochondrial disorders, although an increasing range of tests are available on white blood cells, which has decreased the need for muscle biopsy in the investigation of mitochondrial disorders.
Nerve conduction studies and electromyography (NCV/EMG) should be used to detect concomitant peripheral neuropathy or myopathy.
Electroencephalography (EEG) may be useful for the evaluation of spells suggestive of seizures.
Audiology for the detection of hearing loss can result in early detection and treatment of hearing impairment.
Ophthalomology examination may provide clues to the underlying diagnosis and may also permit early treatment of associated vision impairment.
Patients with conditions involving multiple organ systems should have appropriate investigations for cardiac, renal, and gastrointestinal manifestations.
Semin Neurol. 2012;32(1):29-33. © 2012 Thieme Medical Publishers