Gaucher's Disease Type I. Non neuronopathic type. Glucocerebrosidase (acid betaglucosidase) deficiency.
Incidence
It is an autosomal recessive condition with more than 20,000 cases of Gaucher's disease in the United States and 2/3 are Jewish. This condition is particularly common among Ashkenazi Jews with a prevalence of 1/1000.
Clinical Characteristics
It is the most frequent type of Gaucher's disease. Almost 99 % of all cases of Gaucher's disease are type I. It is of no practical concern to neurologists because only rarely and secondarily involves the nervous system. The disease can be diagnosed as early as in the first week of life or as late as 80 years. Is characterized by intracellular accumulation of glucocerebroside in macrophages, especially in the spleen, liver, bone marrow and lungs. The symptoms of the disease are directly related to the tissue distribution of the pathology. The commonest presentation of the disease is asymptomatic splenomegaly or complications of hypersplenism. Unusual bruising, excessive bleeding during dental surgery or postpartum hemorrhage may be the first indication of marked thrombocytopenia. Anemia and mild neutropenia may be present. Splenomegaly is massive and also liver is very enlarged. Some times there is abdominal pain related to splenic infarcts. The infiltration of bone marrow with storage cells produce expansion of the marrow with thinning of bone cortex producing widening of the end of long bones, producing typical Erlenmeyer flask shape in the distal end of the femurs. Spontaneous fractures are common and often they are bone crisis with sudden onset of severe pain, swelling and tenderness of long bones of lower extremities often associated with fever, very suggestive of osteomyelitis or septic arthritis. Avascular necrosis of the heads of the femurs and humeri is also common. Bone marrow aspiration generally shows the presence of typical Gaucher's storage cells. Diagnosis is confirmed by demonstrating deficiency of betaglucosidase in peripheral blood leukocytes and cultured fibroblasts. Skin pigmentation may be present. There are occasional isolated ocular motor abnormalities. It may be associated myoclonic jerks and seizures. Laboratory diagnosis shows acid betagalactosidase deficiency and elevated serum acid phosphatase. Treatment with IV glucocerebrosidase obtained from placenta or by recombinant DNA technology (alglucerase) every 2-4 weeks produces dramatic improvement of spleen size and hemoglobin and platelets, but bone changes are slower to respond. It is very expensive treatment ($250,000 US for a year of treatment for an affected adult). Cerezyme (imiglucerase) has been approved for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of type 1 Gaucher disease. For more information, contact Genzyme.com.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Bone marrow aspiration generally shows the presence of typical Gaucher's storage cells. Diagnosis is confirmed by demonstrating deficiency of betaglucosidase in peripheral blood leukocytes and cultured fibroblasts. Laboratory diagnosis shows acid betagalactosidase deficiency and elevated serum acid phosphatase.