Gaucher Disease Treatment & Management

  • Author: Ellen Sidransky, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jul 22, 2010
 

Medical Care

Enzyme replacement therapy (ERT) for Gaucher disease is now available, with most patients receiving recombinant enzyme (imiglucerase [Cerezyme]).[3] This preparation is highly effective in reversing the visceral and hematologic manifestations of Gaucher disease. However, skeletal disease is slow to respond, and pulmonary involvement is relatively resistant to the enzyme. Treatment is typically administered once every other week at a high dose, but, in some patients, treatment is administered every week at a medium dose or as many as 3 times per week at low doses. Good responses have been described with all dose regimens, and the issue of the most suitable initial and maintenance dosages remains controversial.

ERT with imiglucerase is indicated for patients with type 1 Gaucher disease who exhibit clinical signs and symptoms of the disease, including anemia, thrombocytopenia, skeletal disease, or visceromegaly. Severity and rate of disease progression widely varies, especially in adults, which makes treatment decisions extremely difficult in some patients. Generally, children who present symptomatically, rather than because of family history, may have severe disease manifestations that require early treatment. Presymptomatic treatment with imiglucerase remains controversial because of the lack of prognostic correlation between genotype and disease severity and the high cost of the therapy.

For most patients with Gaucher disease in the United States, treatment with Cerezyme is typically guided by a geneticist or a hematologist. Patients should receive periodic follow-up at a center familiar with Gaucher disease, if possible.

ERT has a remarkable effect on hepatosplenomegaly, with an average overall decrease of 25% in liver and spleen volume after 6 months of therapy. In most patients with anemia, hemoglobin levels rise by 1.5 g/dL during the first 4-6 months of therapy. An additional increase of 1 g/dL is observed in the subsequent 9-18 months in patients with persistent anemia. The platelet count responds more slowly, doubling on average over 1 year. The hematologic status of patients with splenomegaly must be closely monitored, and splenectomy is still occasionally necessary.

Skeletal disease is the slowest to respond, with symptomatic improvement described by some within the first year of treatment, although a much longer period of ERT is required to achieve a radiologic response. Patients with bone crises require pain relief, hydration, and close monitoring. A bone scan is sometimes needed to differentiate between a bone crisis and infection.

Other effects of ERT in children with Gaucher disease include an increased growth velocity, weight gain, increased energy levels, and a correction of both delayed puberty and hypermetabolic state.

The response of patients to ERT widely varies and does not correlate with genotype, disease severity, splenectomy, or age. However, a number of factors, including cirrhosis and portal hypertension, extensive infarction and fibrosis of the spleen, and lung involvement, portend a poor response to therapy.

The symptoms of patients with Gaucher disease who have associated hematologic malignancies respond relatively poorly to ERT. To overcome these difficulties, increased dosage and frequency of enzyme infusions have been attempted. The symptoms of patients with decompensated liver disease do not appear to respond well to ERT, and these patients remain at risk for life-threatening hemorrhage due to variceal bleeding.

No evidence shows that ERT results in neurologic improvement. Although the enzyme affects the visceral involvement in types 2 and 3 disease, the associated brain involvement may persist or progress.

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Surgical Care

Partial and total splenectomy was once advocated in the treatment of patients with Gaucher disease. However, with the availability of ERT, this procedure is no longer necessary in most patients.

In addition, patients with Gaucher disease may require hip replacements or other orthopedic procedures to treat skeletal disease. This is best undertaken after the patient has undergone several months of ERT.

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Consultations

Consultations with the following specialists are indicated:

  • Medical geneticist
  • Hematologist
  • Orthopedist
  • Neurologist
  • Neuro-ophthalmologist
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Diet

No dietary manipulation has been found to affect disease progression.

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Activity

Patients with massive splenomegaly or severe thrombocytopenia should avoid contact sports and any other activities that place them at risk for splenic rupture or bleeding

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Contributor Information and Disclosures
Author

Ellen Sidransky, MD  Senior Investigator, Chief, Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH

Ellen Sidransky, MD is a member of the following medical societies: American Society of Human Genetics, Movement Disorders Society, Society for Inherited Metabolic Disorders, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert D Steiner, MD  Professor, Departments of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Oregon Health and Science University School of Medicine; Director and Consulting Staff, Metabolic Bone Disease Clinic, Shriner's Hospital and Doernbecher Children's Hospital; Co-Director of Pediatric and Child Health Research, Oregon Clinical and Translational Research Institute (CTSA)

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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