Diagnosis of atypical patients with lipid storage diseases

Abstract

Typical patients with lipid storage diseases can usually be diagnosed by measurement of the enzyme in question. A low enzymatic activity would make the diagnosis and open the way to prenatal testing. However, some problems have become apparent. There are patients who have typical clinical features and storage material but normal enzyme values. This is true of cases of GM2 gangliosidosis and metachromatic leukodystrophy. Some patients are missing a heat stable protein required for interaction between the lipid substrate and the lysosomal enzyme. These so-called "sphingolipid activator proteins" were isolated and antibodies were produced in rabbits. A test of cross-reacting material in easily obtained tissue samples has resulted in new methods for diagnosis. The use of a sulfated derivative of 4-methylumbelliferyl-β-D-N-acetylglucosaminide has allowed the diagnosis of new patients with GM2 gangliosidosis. The finding of healthy people with enzyme values near those of affected patients has caused problems with accurate diagnosis. However, the use of ¹⁴C-stearic acid-labeled sulfatide in the medium of cultured skin fibroblasts has allowed clear identification of affected and non-affected people both pre- and postnatally. New methods for diagnosis have resulted in improved health care to those families with a lipid storage disease.