There is a vast spectrum of clinical manifestations encountered in individuals with lysosomal storage diseases. Lysosomes are organelles that are involved in the degradation of intracellular proteins, recycled products and organelle in the cell. Lysosomal storage disorders occur when an enzyme necessary for breaking down these molecules is deficient, and, as a result, the substrate accumulates within the lysosomes of cells and may affect different organ systems. This is a longitudinal natural history study of patients with Gaucher disease and other storage disorders. Gaucher disease, the most common lysosomal storage disorder, results from the inherited deficiency of the enzyme glucocrebrosidase, which breaks down the lipid glucocerebroside. The disease is characterized by the continuum of phenotypes. The severity is extremely variable, with some patients presenting in childhood with virtually all the complications of Gaucher disease, while others remaining asymptomatic into their eighth decade. Often patients with Gaucher disease develop hepatosplenomegaly, anemia, thrombocytopenia and bony problems. Gaucher disease has traditionally been divided into three clinical subtypes, delineated by the absence or presence of neurologic involvement and it progression:

Type 1 - Non-neuronopathic form

Type 2 - Acute neuronopathic form

Type 3 - Chronic neuronopathic form

Some patients, how ever defy classification into these three categories

Our specific aim in this study is to identify genetic, biochemical and clinical parameters that are associated with disease severity in individuals with lysosomal storage disorders, and to explore the natural history and extent of associated clinical manifestations. Participants will be evaluated at the NIH to better characterize the clinical, genetic and pathophysiological features of these disorders. In order to better understand the entire effect of the enzyme deficiencies and the function of the particular proteins involved, emphasis will be placed on individuals with atypical presentations. In particular, we will focus on subjects with Gaucher disease and parkinsonism, to better understand the association between the two disorders. Following an initial comprehensive workup, participants will be studied as either in the inpatient unit or the outpatient clinic, and will be re-evaluated at approximately one-year intervals.