Table 87-1System Involvement ||Download (.pdf) Table 87-1 System Involvement
|System ||Manifestation |
|Skeletal ||Marrow infiltration, Erlenmeyer flask deformity, lytic lesions, bone infarcts, avascular necrosis, and low bone density |
|Visceral ||Hepatosplenomegaly |
|Hematologic ||Cytopenias and acquired coagulation factor abnormalities |
|Pulmonary ||Pulmonary hypertension |
|Immunologic ||Polyclonal or monoclonal gammopathy |
|Metabolic ||Low total and HDL cholesterol, high ferritin, elevated chitotriosidase, and angiotensin-converting enzyme levelsa |
|Neurologic ||Types 2 and 3 disease: psychomotor retardation, opisthotonus, oculomotor apraxia, retroflexion, spasticity |
|Cardiovascular ||Homozygosity for the D409H mutation confers an atypical phenotype with valvular calcification |
Diagnostic Criteria and Clinical Characteristics
Diagnosis is established by
Determining the acid β-glucosidase enzyme activity in peripheral blood leucocytes is diagnostic for all subtypes. Affected individuals will have activity which is markedly decreased to less than 10% of normal mean activity. Enzyme activity does not differentiate the subtypes or predict disease severity.
Mutation analysis of the five most common mutations (N370S, L444P, 84GG, IVS2+1, and R496H) in the acid β-glucosidase gene will detect over 95% of mutations in Ashkenazi Jewish patients and around 50% to 60% in non-Jewish patients. DNA sequencing of the acid β-glucosidase gene will identify other mutations, and mutation analysis can predict disease subtype and prognosis.
Bone marrow ...