ABSTRACT
Lysosomal storage disorders (LSDs) constitute a group of genetic diseases caused by defects in genes that control the lysosomal degradation of naturally occurring proteins, glycoproteins, sphingolipids, glycosaminoglycans (GAGS) and carbohydrates, and the transport of certain smaller molecules from the lysosomes. The birth of an individual affected with an LSD is estimated to occur in about 1 in 5000-8000 births in the United States and Europe (1). Therefore, about 500-800 potential patients are born each year in the United States. While some disorders manifest in utero with features such as hydrops, others do not have recognizable symptoms until the eighth or ninth decade. Over 40 different genes are involved in these diseases, and most are inherited in an autosomal recessive (AR) manner. Many diseasecausing mutations and polymorphic changes have been identified in these genes, and many patients are compound heterozygotes, having different mutations in the two copies of the same gene. This results in the wide range of clinical features that is characteristic of most LSDs and is responsible for the difficulty in predicting the clinical course in newly diagnosed patients, especially those with juvenile and adult onset. While neurological symptoms are found in many patients with a LSD, the age of onset, level of impairment and disease progression are quite variable. The accurate diagnosis of patients, especially those early in the course of their disease, is a challenge for both
the clinician and laboratory performing diagnostic testing. As the clinical features observed frequently overlap both among the different LSDs and with other genetic and non-genetic disorders, a wide range of testing might be indicated after examination of a patient. Testing for most LSDs is relatively straight-forward and can result in a definitive diagnosis within a short period of time. This usually entails the measurement of enzymatic activities by using synthetic or natural substrates in easily obtained tissue samples, detection of an abnormal level of a metabolic product in cells or urine, or identification of a known mutation(s) in certain families or within certain ethnic groups.
