Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months

Abstract Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.

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Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months

Blood ◽

10.1182/blood.v82.2.408.bloodjournal822408 ◽

1993 ◽

Vol 82 (2) ◽

pp. 408-416 ◽

Cited By ~ 1

Author(s):

GM Pastores ◽

AR Sibille ◽

GA Grabowski

Keyword(s):

Gaucher Disease ◽

Enzyme Therapy ◽

Lysosomal Storage ◽

Ashkenazi Jews ◽

Gaucher Disease Type 1 ◽

Beta Glucosidase ◽

Age Range ◽

Different Doses ◽

Dose Reductions

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.

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Enzyme Therapy in Gaucher Disease Type 1: Effect of Neutralizing Antibodies to Acid β-Glucosidase

Blood ◽

10.1182/blood.v90.1.43 ◽

1997 ◽

Vol 90 (1) ◽

pp. 43-48 ◽

Cited By ~ 48

Author(s):

Elvira Ponce ◽

Jay Moskovitz ◽

Gregory Grabowski

Keyword(s):

Disease Progression ◽

Gaucher Disease ◽

Neutralizing Antibodies ◽

Disease Type ◽

High Dose ◽

Enzyme Therapy ◽

Lysosomal Storage ◽

Gaucher Disease Type 1

Abstract Gaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid β-glucosidase locus. Periodic infusions of macrophage-targeted acid β-glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid β-glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid β-glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid β-glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid β-glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.

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Enzyme Therapy in Gaucher Disease Type 1: Effect of Neutralizing Antibodies to Acid β-Glucosidase

Blood ◽

10.1182/blood.v90.1.43.43_43_48 ◽

1997 ◽

Vol 90 (1) ◽

pp. 43-48 ◽

Cited By ~ 1

Author(s):

Elvira Ponce ◽

Jay Moskovitz ◽

Gregory Grabowski

Keyword(s):

Disease Progression ◽

Gaucher Disease ◽

Neutralizing Antibodies ◽

Disease Type ◽

High Dose ◽

Enzyme Therapy ◽

Lysosomal Storage ◽

Gaucher Disease Type 1

Gaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid β-glucosidase locus. Periodic infusions of macrophage-targeted acid β-glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid β-glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid β-glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid β-glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid β-glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.

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Individualized long-term enzyme therapy for Gaucher disease type 1 in Slovenia

Pediatrics International ◽

10.1111/j.1442-200x.2011.03451.x ◽

2011 ◽

Vol 53 (6) ◽

pp. 1018-1022 ◽

Cited By ~ 1

Author(s):

Majda Benedik-Dolničar ◽

Lidija Kitanovski

Keyword(s):

Gaucher Disease ◽

Disease Type ◽

Enzyme Therapy ◽

Gaucher Disease Type 1

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Finding and Treating Gaucher Disease Type 1 – The Role of the Haematologist

European Oncology & Haematology ◽

10.17925/eoh.2018.14.1.50 ◽

2018 ◽

Vol 14 (1) ◽

pp. 50

Author(s):

Maria-Domenica Cappellini ◽

Elena Cassinerio ◽

Irene Motta ◽

William Morello ◽

Jesús Villarubia

Keyword(s):

Gaucher Disease ◽

Clinical Symptoms ◽

Genetic Disorder ◽

Diagnostic Delay ◽

Screening Tools ◽

Substrate Reduction Therapy ◽

Lysosomal Storage ◽

Ashkenazi Jews ◽

Enzyme Replacement

Gaucher disease (GD) type 1 is the most common lysosomal storage disease and the most common genetic disorder among Ashkenazi Jews. The majority of patients with GD present with unexplained splenomegaly and/or thrombocytopenia, and the disorder often affects children; consequently, haematologists and paediatricians are ideally placed to diagnose this condition. Prompt management of GD type 1 using enzyme-replacement therapy or substrate reduction therapy can reduce the risk of developing long-term GD complications and reverse many of the initial signs/symptoms, thereby improving both quality and duration of life. Treatment is most effective when initiated early; consequently, a prompt diagnosis is essential. Despite this, the average time to diagnosis following the onset of clinical symptoms is 4 years. Reasons for the delay include the heterogeneous nature of the disease, together with a lack of awareness of rare haematological disorders and the benefits of early treatment. Indeed, studies show that only 20% of haematologists consider GD type 1 in their differential diagnosis for patients presenting with splenomegaly and/or thrombocytopenia. To help raise awareness of GD, reduce the diagnostic delay and prevent unnecessary tissue biopsies, simple diagnostic algorithms and screening tools have been developed and validated, both in adults and in children.

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Gaucher Disease: Case Report

Journal of Bioscience & Biomedical Engineering ◽

10.47485/2693-2504.1033 ◽

2021 ◽

Keyword(s):

Gaucher Disease ◽

Autosomal Recessive ◽

Genetic Disorder ◽

Autosomal Recessive Inheritance ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Disease Case ◽

Gaucher Disease Type 1 ◽

The Common

Gaucher disease is the most common lysosomal storage disease. It is marked by deficient glucocerebrosidase enzyme activity, leading to elective accumulation of its substrate in the lysosomes of macrophages. Macrophages are most often deposited in the liver, spleen and bone marrow, creating typical symptomatology in these organs. It is a genetic disorder with autosomal recessive inheritance pattern. The extent of the damage and severity of the symptoms increase in proportion to the genetic damage in the culprit gene, GBA1. As a result, the symptoms and course of the disease may range from mild to quite acute, with potential death of the patient at a young age. Case: Patient, 29, was diagnosed with Gaucher disease type 1 and underwent enzyme replacement therapy, with satisfactory response. Along with the common symptoms of the disease, he had also developed the rare Erlenmeyer flask deformity.

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Coxarthritis as the Presenting Symptom of Gaucher Disease Type 1

Arthritis ◽

10.1155/2011/361279 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Giacomo Brisca ◽

Maja Di Rocco ◽

Paolo Picco ◽

Maria Beatrice Damasio ◽

Alberto Martini

Keyword(s):

Gaucher Disease ◽

Lysosomal Storage Disorder ◽

Signs And Symptoms ◽

Mononuclear Phagocyte ◽

Disease Type ◽

Lysosomal Storage ◽

Skeletal Disease ◽

Abnormal Accumulation ◽

Gaucher Disease Type 1

Gaucher disease (GD) type 1 is the most common lysosomal storage disorder due to beta glucocerebrosidase deficiency leading to an abnormal accumulation of its substrate, glucocerebroside, in the mononuclear phagocyte system. The disease presentation is usually characterized by signs and symptoms related to hypersplenism, such as splenomegaly, anaemia, thrombocytopenia and leucopenia. Skeletal disease may occur later for the infiltration of bone marrow by macrophages infiltration and bone resorption: bone involvement may be heterogeneously manifested by symptoms ranging from bone crisis to avascular necrosis, osteoporosis and defect in remodeling of long bones. Herein, we report a patient in whom the osteoarticular involvement has been the only symptom of the disease stressing that this unusual presentation of GD has prompted a wide differential diagnosis with more common forms of coxitis.

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Gaucher disease: masquerading as chronic malaria

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20182588 ◽

2018 ◽

Vol 5 (4) ◽

pp. 1688

Author(s):

Seema Rai ◽

Gurmeet Kaur Sethi ◽

Rama Kumari ◽

Varun Kaul

Keyword(s):

Gaucher Disease ◽

Bone Marrow Involvement ◽

Disease Type ◽

Neurological Involvement ◽

Type Ii ◽

Lysosomal Storage ◽

Lysosomal Disorder ◽

History Of ◽

Gaucher Disease Type 1

Gaucher disorder s rare lysosomal disorder characterized by glycolipid laden lysosomes leading to hepatosplenomegaly, bone marrow involvement. Three types of Gaucher disease have been described based on the clinical features, ethnicity and the natural history of the disease. Gaucher disease Type 1 (GD1) occurs mainly in infancy to adulthood and is the commonest lysosomal storage disorder. Gaucher Disease Type II (GD2) and Gaucher disease type III (GD3) patients have onset at less than 1 year, and 2-20 years, respectively.1 GD1 patients do not have neurological involvement. GD2 is the acute neuronopathic and GD3 is the chronic neuronopathic type.

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