Multiple forms of membrane-bound β-glucosidase in Gaucher's disease

Two forms of membrane-bound β-glucosidase in the spleen of normal individuals were distinguished by their thermostability properties. The heat-labile form A predominates; it catalyzes the hydrolysis of the natural substrate, glucosylceramide, and is activated by the detergent, sodium taurocholate. The minor heat-stable form B is inactive against glucosylceramide and is inhibited by taurocholate. The activity of form A increases from childhood to adult life, as does the activity of the soluble β-glucosidase and of glucosylceramide β-glucosidase. In the spleen of nine patients with different types of Gaucher's disease the residual membrane-bound β-glucosidase was predominantly heat-stable and inhibited by taurocholate. There was no clear correlation between the properties of the residual enzyme in the different types of the disorder and their respective clinical severity. The results are discussed in relation to the biochemical pathogenesis and the enzymatic diagnosis of Gaucher's disease.     

Unexpected splenic nodules in leukemic patients

We reviewed a series of five splenectomy specimens from patients with various leukemias (three cases of chronic myelocytic leukemia, one case of acute myelocytic leukemia, and one case of hairy cell leukemia). In addition to diffuse red pulp disease, we unexpectedly encountered nodules grossly in each of the specimens. These represented sea blue histiocytosis (one case), focal hairy cell leukemia (one case), localized blast transformation (one case), and concentrated foci of treated leukemia (two cases), with a prominence of immature granulocytic precursors on a background of trilineage hyperplasia. These cases are reported because they are unusual and because they furnish interesting correlates of gross and microscopic anatomy.     

Activator protein deficient Gaucher's disease

Summary A report is presented based on the biochemical and immunochemical studies of various tissues from a 15-year-old boy with a neuronopathic form of Gaucher's disease. Qualitative and quantitative lipid analyses revealed a storage of glucosylceramide. The striking feature was that, employing the usual assay methods, a normal activity of the lysosomal enzyme glucosylceramidase was revealed, despite massive lipid accumulation. Immunochemical assays of hepatic and splenic tissue extracts from this atypical Gaucher's patient disclosed the absence of A₁ activator protein, which is necessary for the enzymic degradation of glucosylceramide in vivo. This is the second documented case of a patient presenting with glucosylceramide activator protein deficiency.     

Coexistence of Hodgkin's disease and Gaucher's disease.

A case of Hodgkin's disease associated with long-standing Gaucher's disease is presented and compared with the only previously reported case. The two diseases coexisted in lymph nodes both above and below the diaphragm, liver, bone marrow, and pancreas. The question of a possible relationship of the two diseases is discussed.     

Bone-marrow transplantation in severe Gaucher's disease

We performed allogeneic bone-marrow transplantation of normal cells in an eight-year-old patient with Type 3 Gaucher's disease in an attempt to alter his progressive deterioration. The procedure resulted in complete engraftment of the enzymatically normal donor cells. Donor monocyte precursors were present in the circulation of the recipient by 28 days after transplantation. Post-transplantation beta-glucocerebrosidase activity in mononuclear white cells in peripheral blood exceeded normal levels. Despite these early results no change in Gaucher's-cell infiltration of the bone marrow was noted for at least 111 days, and Gaucher's cells persisted in the marrow for at least 274 days. The plasma glucocerebroside concentration ultimately returned to normal. During the post-transplantation course, until the patient died from an episode of sepsis, there was no important change in his clinical status. However, this case demonstrates that the enzymatic abnormality in hematopoietic cells in Gaucher's disease is correctable by bone-marrow transplantation, leading to normalization of plasma levels of glucocerebroside. We observed the long survival of Gaucher's cells, which was consistent with the lack of clinical improvement. Intervention might have been more effective earlier in the course of the disease.     

Autoimmune hemolytic anemia in Gaucher's disease

Summary A 23-year-old Ashkenazi woman with Gaucher's disease developed Coombs-positive warm-type autoimmune hemolytic anemia. Treatment with high-dose steroids resulted in complete remission within 2 weeks. Study of an additional 72 patients with Gaucher's disease revealed another case of Coombs-positive warm-type autoimmune hemolytic anemia; other autoimmune disorders were found in 17 of these patients. The possible association of Coombs-positive hemolytic anemia and Gaucher's disease is discussed.     

Pulmonary pathology in Gaucher's disease.

Gaucher's disease is a familial storage disease caused by a deficiency of the enzyme glucocerebrosidase. Pulmonary involvement is considered rare in Gaucher's disease, especially type I. Sporadic case reports have shown various types of lung involvement, but the spectrum of pulmonary pathology in Gaucher's disease has not been described. Nine cases of Gaucher's disease were retrieved from the autopsy file of Hadassah Medical Center, Jerusalem, Israel. There were six cases with type I Gaucher's disease and three cases with type II. Lung sections were evaluated, and special stains were employed, including immunohistochemical stains for CD68, cytokeratin, and CD34. Gaucher cells were found in the lungs in all nine cases. The involvement was considered pathologically significant in five of nine cases and clinically significant in three of nine cases. Four distinct patterns of pulmonary involvement by Gaucher cells emerged: intracapillary (9 of 9), patchy interstitial infiltrates in a lymphatic distribution (2 of 9), massive interstitial thickening of alveolar septa (1 of 9), and intra-alveolar infiltrates (2 of 9). The universal involvement of pulmonary capillaries indicates that this is probably systemic in nature and not intrinsic to the lungs. Pulmonary involvement in Gaucher's disease is commoner than previously recognized. Immunocytochemical stains help to identify isolated Gaucher cells and distinguish them from native alveolar macrophages.     

Infantile neurological Gaucher's disease in three siblings

Summary The clinical, histological and histochemical aspects of infantile neurological Gaucher's disease in three siblings are described.In one of them, electron-microscopic examination of Gaucher cells from a cervical lymphnode biopsy was carried out. We believe that the term tubes is inadequate to describe Gaucher bodies, since we have shown that most Gaucher bodies consist of flattened sac-like structures. A fragment of the cerebral cortex obtained from the same subject four hours after death was also studied with the electron microscope; surprisingly, Gaucher bodies were observed in some neurons.The various factors which can favour the deposition of kerasin are discussed.     

Gaucher's disease: report of 4 cases

Review of records for last 5 years has shown 4 cases of Type I Gaucher's disease in our institute. The cases were diagnosed on bone marrow aspiration, examination of splenectomy specimen, liver biopsy and post mortem in one case. The age range was 2 years to 22 years. Male to female ratio was 3:1.Splenectomy was performed in one case and one case received enzyme replacement therapy with high dose, low frequency regimen for six months without any favorable effect. All were Hindus. Family history of similarly affected and treated twin brother was available in one case. The predominant clinical presentation was pancytopenia and splenohepatomegaly with splenomegaly greater than hepatomegaly. Remarkable constitutional inferiority was noted in one case, which succumbed to death following acute illness and bleeding diathesis. Post mortem performed showed infiltration of spleen and liver with Gaucher cells, fibrosis and myeloid metaplasia in liver and lung.     

Beta-glucosidases. Molecular bases of Gaucher's disease

The first part of this review deals the biochemical data concerning human and mammalian beta-glucosidases. Glucosylceramide-beta-glucosidase and non-specific beta-glucosidase are characterized following their physical, functional, structural and genetical properties. The second part deals with the biochemical and pathophysiological data concerning the Gaucher disease.