The lysosomal storage diseases are a group of about 40 different diseases, each characterised by a specific lysosomal enzyme deficiency in a variety of tissues. They occur in total in about 1 in 5,000 live births and display considerable clinical and biochemical heterogeneity. The majority are inherited as autosomal recessive conditions although two (Hunter disease and Fabry disease ) are X-linked. The SAS laboratory offers a very comprehensive service for these disorders, and also has a major research interest in them.
Lysosomal enzymes are normally involved in the intracellular degradation of macromolecules to low molecular weight compounds. Deficiencies of these enzymes result in the accumulation of undegraded macromolecules within the lysosomes, leading to the subsequent pathological features of the disease. Usually there is a specific enzyme deficiency (eg of hexosaminidase A in Tay-Sachs disease ), but there may be a failure of delivery of enzymes to the lysosomes (eg I-cell disease), defective transport of a small molecule out of lysosomes (eg cystinosis) or deficiency of a small molecular weight protein that participates in degradation of sphingolipids (eg saposin B deficiency).
Clinical diagnosis of these disorders is often difficult because the features lack specificity, and histopathological techniques are limited because they will not usually distinguish between different types of storage material. Enzymatic diagnosis offers the chance of a definitive result, and also makes possible prenatal diagnosis in future pregnancies in the family. A list of the diseases for which tests can be carried out is given below, together with specimen requirements and availability of prenatal diagnosis (PND). In addition to single enzyme assays we offer groups of assays as screening procedures depending on clinical features (lysosomal enzyme screening), or a systematic routine using urine and blood which should confirm or exclude the great majority of disorders. This routine includes analysis for urinary glycosaminoglycans and oligosaccharides, which are also available as separate tests.
Some features that should lead to suspicion of a lysosomal disorder and which should be mentioned when sending specimens include the following:
- unexplained neonatal ascites or hydrops fetalis; cardiomyopathy with hypotonia; hepato(spleno)megaly;
- coarse facies; skeletal dysplasia with or without short stature; joint stiffness; hirsuitism;
- vacuolated lymphocytes; progressive neurological degeneration; cherry-red spot or corneal clouding;
- vertical supranuclear ophthalmoplegia; peripheral neuropathy; leucodystrophy on CT scan;
- myoclonic jerks; ataxia; angiokeratoma corporis diffusum.
Lysosomal Storage Disorders for which tests can be carried out:
- Mucopolysaccharidoses (MPS)
- Glycogen storage disease
- Lysosomal enzyme processing defects
- Transport defects
- Other lysosomal disorders