This may represent involvement by Gaucher's disease. Similar histiocytic cells (pseudo-Gaucher cells) may be seen in other diseases including CML, CLL, and Thalassemia major. Features of these entities are not present in the bone marrow.
Note: The level of beta-glucocerebrocidase was subsequently found to be 3 nmoles/mg protein/hour [normal range 18-23 nmoles/mg protein/hour] consistent with the diagnosis of Gaucher's disease.
Gaucher Disease is a rare autosomal recessive disorder characterized by defective function of the catabolic enzyme beta-glucocerebrocidase leading to an accumulation of glucocerebroside in cells of the monocyte-macrophage system. The disease is estimated to affect 10 - 20,000 people in the United States. Although rare, Gaucher disease is the most common sphingolipid storage disorder and the most common genetic disorder in persons of Ashkenazic Jewish origin. The disease is also seen among non-Jewish caucasians as well as natives of Greece, India, China, and Japan.
The phenotype has been divided into three major types based on clinical signs/symptoms (See Table 1). The phenotype even within these types can be quite heterogenous. For example, the Adult form (Type I), which is the most common type of Gaucher's disease, often presents with a combination of anemia, thrombocytopenia, hepatosplenomegaly, and extensive skeletal disease. However, other Type I patients (and this case in particular) may have no symptoms and can be identified only by screening or during evaluation for other diseases(e.g. anemia).
The varied clinical phenotype of Gaucher's disease is probably due to the fact that a large number of mutations produce the disease. To date, 36 mutations of the beta-glucocerebrocidase gene has been discovered. The gene is located on chromosome 1.
|Type I, non-neuronopathic (adult)||Hepatosplenomegaly (Inconspicuous or absent), Adenopathy (Minimal), Ascites (Rare), Hemmorhage from nose/gums (Common), Petechiae/Puperic spots (Occasional), Skin Pigmentation (45-75% of patients), Pingueculae, Bone Destruction (75% esp. the femur), Onset is early in life with mild/minimal symptoms/signs, Anemia, thromboctopenia, and/or bone lesions often lead to diagnosis|
|Type II, acute neuronopathic (infantile)||Retarded developement, Early onset of the neurologic symptoms, Hepatosplenomegaly, Cachexia, Death before age 2|
|Type III, subacute neuronopathic (juvenile)||Onset at 6 months to one year of age, Later onset (than Type II) of the neurologic symptoms, 50% survival to late childhood teenage years|
Horowitz M. Zimran A., Mutations Causing Gaucher Disease, Human Mutation, 3(1):1-11, 1994.
Beutler E., Gaucher Disease: New Molecular Approaches to Diagnosis and Treatment, Science 256(5058):794-9, 1992.
Contributed by Curtis Goldblatt, M.D.