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Gaucher's disease: a review for the internist and hepatologist
1Department of Medicine, St. Josef-Hospital Oberhausen, University of Essen, Germany. claus.niederau@uni-duesseldorf.de
Insights
Gaucher's disease, a genetic disorder, requires increased physician awareness for timely diagnosis and treatment. Enzyme replacement therapy offers significant improvements for patients with type 1 Gaucher's disease.
Area of Science:
- Biochemistry
- Genetics
- Internal Medicine
Background:
- Gaucher's disease is an autosomal recessive lysosomal storage disorder caused by glucocerebrosidase deficiency.
- It leads to glucocerebroside accumulation, causing multi-systemic effects with a prevalence of 1:30,000–1:50,000.
- Limited physician awareness hinders diagnosis and treatment, despite available diagnostic tests.
Purpose of the Study:
- To provide internists and hepatologists with practical information on managing non-neuronopathic type 1 Gaucher's disease.
- To highlight recent advances in diagnosis and treatment strategies.
- To increase awareness of the disease and its management.
Main Methods:
- Review of current literature on Gaucher's disease management.
- Focus on diagnostic criteria, including enzyme assays and biopsy findings.
- Discussion of enzyme replacement therapies (alglucerase, imiglucerase) and gene therapy trials.
Main Results:
- Type 1 Gaucher's disease should be suspected with unexplained splenomegaly, hepatomegaly, anemia, thrombocytopenia, or skeletal issues.
- Diagnosis is confirmed by glucocerebrosidase enzyme activity assay in leukocytes.
- Enzyme replacement therapy with imiglucerase shows efficacy in improving hematological, organomegaly, and quality-of-life parameters within months.
Conclusions:
- Early diagnosis and management of Gaucher's disease are crucial for improving patient outcomes.
- Enzyme replacement therapy is effective for type 1 Gaucher's disease, with long-term benefits for skeletal complications.
- Gene therapy represents a promising future direction for Gaucher's disease treatment.
Abstract:
Gaucher's disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multi-system disease which prevalence ranges between 1:30,000 and 1:50,000 in most countries. Thus only a minority of physicians are aware of this diagnosis, of the symptoms that should lead to its consideration, and of the availability of specific tests that confirm it. Because Gaucher's disease often affects the liver, hepatologists may care for Gaucher patients. This review provides the internist and hepatologist with practical information about recent advances in the management of the non-neuronopathic type I of Gaucher's disease. Gaucher's disease, type 1 should be considered when unexplained spleno- and hepatomegaly, anemia, thrombocytopenia, or skeletal disease are present, particularly in combination. The diagnosis is established by an assay for glucocerebrosidase activity in peripheral leukocytes. Lack of awareness and of widespread availability of the enzyme assay has as yet limited its application in clinical practice, and led to many cases of Gaucher's disease being diagnosed by bone marrow and liver biopsy. Alglucerase, placental enzyme preparation of glucocerebrosidase, has proven effective in more than 1,000 patients worldwide. Recently, alglucerase has been exchanged by the recombinant enzyme preparation imiglucerase, which is equally effective and safe. Enzyme replacement improves hematological abnormalities, hepato-splenomegaly, and quality of life in a matter of a few months. Regression of skeletal complications is usually seen only after 3-4 years. Recently gene therapy trials, which center on autotransfusion of retrovirally transduced stem cells, have successfully been started.