PubMed1976
The disorders presented consist of those clinical entities in which a reasonably well defined lipid storage material accumulated within nervous tissue. Many other progressive, degenerative disorders are suspected of being storage disorders, but their chemical pathology remains unclear. Collectively this group could be designated the sphingolipidoses. In each case, the disease is a genetic disturbance and transmitted as an autosomal recessive. Sphingolipid storage in each disorder is associated with deficient activity of a specific degradative enzyme or enzyme system, and these deficient enzymes are all lysosomal hydrolases. Lysosomal hydrolases catalyze the breakdown of complex molecules in digestive vacuoles (phagocytic or autophagic) within the cells. Lysosomes show structural latency (requiring osmotic shock or freeze thawing in vitro); their enzymes show maximal activity at acidic pH ranges, and on electron microscopic examination they appear as small, electron-dense intracellular bodies. These hydrolytic enzymes seem to have some form of biological vulnerability in terms of their genetic expression, and this vulnerability underlies the sphingolipidoses. Diagnosis in each case is primarily a clinical problem. The presentation of these disorders, especially in intermediate or advanced forms, is sufficiently distinctive to permit a reasonably accurate diagnosis on the basis of history, physical examination, and routine laboratory data. Patients seen in early stages may be more difficult to recognize but follow-up evaluations usually clarify the problem. Specific enzyme assays are now available for confirmation of the diagnosis in these disorders. A frequent finding in this connection is an increase in the activities of noninvolved lysosomal hydrolases in the storage disorders. Once a case is clinically diagnosed, the clinician has the responsibility of ensuring that proper genetic counseling is made available to the affected families. Considerable supportive care is needed in each case. These patients can survive for prolonged periods, and great stress is placed on their families by these prolonged, hopeless illnesses. Since the disorders affect infants or young children, their parents are usually young adults in their early reproductive years. It is essential that they receive information concerning the risk of subsequent pregnancies. Specific diagnosis of the fetus in early pregnancy can be made now by amniocentesis and enzyme assays on cultured fibroblasts. If the fetus is a homozygote on the basis of enzyme assays, the option of therapeutic abortion should be discussed with the family. For many parents there will be considerable sensitivity to the ethical implications of this course and, if any doubt arises, ethical or pastoral consultation should be sought. Although there are no specific therapeutic approaches, a considerable degree of supportive care can and should be given. In the gangliosidoses and late in the course of the leukodystrophies, seizures will present management problems...