More specialised Round 2 investigations
| Test | Comments |
|---|---|
| Blood | |
| Plasma amino acids | Separate sample without delay and freeze for transport or while awaiting analysis. Avoid haemolysis |
| Very long chain fatty acids | Preferably a preprandial or fasting sample |
| White cell (leukocyte) enzyme activity | Laboratories may group these tests according to clinical features and so it is essential to provide good clinical details and age of onset of symptoms. A group of enzyme assays can be carried out on a single blood sample which provides both white blood cells and plasma for analysis. If a specific enzyme deficiency is suspected then discuss with your local enzyme laboratory in order to prioritise particular assays. Some enzymes cannot be assayed in leukocytes and skin fibroblasts will be required instead. Depending on the clinical picture and other biochemical results, the enzymes to be assayed include: galactocerebosidase, arylsulfatase A, β-hexosaminidase A, glycogen debrancher enzyme, α-mannosidase and aspartoacylase (table 1) |
| Cholestanol profile | |
| Urine | |
| Organic acids | Random sample, with no preservatives, early morning if possible as it is likely to be a more concentrated sample. List all medications on the request form to aid interpretation. Freeze sample for transport or prolonged storage |
| Bile alcohols | |
| Biopsy | |
| Axillary skin biopsy | Electron microscopy of biopsy helpful in the diagnosis of CADASIL |
| Sural nerve biopsy | Can be useful in those leukodystrophies associated with peripheral neuropathies, eg, in adult onset polyglucosan body disease intra-axonal polyglucosan bodies are seen. On electron microscopy, these should be located within mylinated nerves |
| Muscle biopsy | See text for further information |
| Brain biopsy | See text for further information |
CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.