Lipid Storage Disorders Treatment & Management

  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Sep 30, 2010
 

Medical Care

  • Except for Gaucher and Fabry disease, treatment options are limited in patients with lipid storage disorders. Primarily, treatment is directed at symptomatic relief. No specific treatment is available for either form of GM1 gangliosidosis, Tay-Sachs disease, Sandhoff disease, fucosidosis, Krabbe disease or Schindler disease. These disorders pursue a relentless course, leading to death.
  • When possible, patients with Gaucher disease should be managed by a multidisciplinary team at a comprehensive Gaucher Center. Enzyme replacement therapy with recombinant beta-glucocerebrosidase (Cerezyme, Genzyme, Cambridge, Mass; VPRIV, Shire, Cambridge, Mass) is available for the treatment of symptomatic patients with Gaucher disease type 1.
    • Regular intravenous infusions of recombinant enzyme have been shown to clear the stored substrate GL1, and thus reverse hematologic and liver/spleen involvement. Although skeletal disease is slower to respond, early treatment may be efficacious in normalizing linear growth and bone morphology in affected children.
    • Although enzyme replacement does not alter the neurologic progression of patients with Gaucher disease types 2 and 3, it has been used in selected patients as a palliative measure, particularly in patients with severe visceral involvement. Individuals with severe visceral symptoms due to Gaucher disease type 3 often benefit from bone marrow transplantation. In some individuals, a combination approach using both enzyme replacement therapy and bone marrow transplant has been used. However, the use of bone marrow transplant is limited due to the associated morbidity and mortality.
    • Alternative treatments are also being evaluated, including substrate reduction therapy, and gene therapy. Miglustat (Zavesca, Actelion, South San Francisco, Calif), an inhibitor of glucosylceramide synthase and alpha-glucosidase, is licensed for the oral treatment of adult patients with mild-to-moderate type 1 Gaucher disease for whom intravenous recombinant enzyme is unsuitable. Its mode of action is to balance the overall level of glucosylceramide by reducing its production to a level comparable with its breakdown by residual glucocerebrosidase activity. Treatment with miglustat may only be approved for patients as a switch from enzyme replacement therapy after reaching maintenance therapy. Studies are currently underway to investigate the use of miglustat for the treatment of infantile-onset GM2 gangliosidosis and childhood Niemann-Pick type C.
  • Until recently, treatment for Fabry disease has been nonspecific and limited to supportive care. These measures included the use of phenytoin and carbamazepine, which have been shown to decrease the frequency and severity of the chronic acroparesthesias and the periodic crises of excruciating pain. Renal transplantation and long-term hemodialysis also have become life-saving procedures for patients with renal failure.
  • More recently, clinical trials with recombinant alpha-galactosidase A (Replagal, TKT Corporation, Cambridge, Mass; Fabrazyme, Genzyme Corporation, Cambridge, Mass) have demonstrated the safety and effectiveness of enzyme replacement therapy for Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement therapy, reversal in lipid tissue storage, and stabilized or improved renal and cardiac function. Subjective reduction or relief from neuropathic pain has been documented, in addition to a decrease in the long-term use of neuropathic pain medication.
  • Recent advances in recombinant enzyme replacement, bone marrow transplantation, gene transfer, substrate reduction, and chaperone-mediated therapy provide great hope in potentially treating other lipid storage disorders.
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Consultations

  • Patients thought to have a lipidosis should have an evaluation with a clinical geneticist.
  • Neurologic consultation also is indicated.
  • Patients with Fabry disease should have a cardiac evaluation.
  • Patients with Gaucher disease type 1 and NPD type B should have pulmonary consultations.
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Diet

  • No specific dietary manipulations have an effect on the disease course. In particular, restriction of lipids is of no benefit.
  • Patients with NPD have elevated total cholesterol, although effects of dietary restriction of cholesterol have not been demonstrated.
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Activity

  • Gaucher disease and patients with NPD with organomegaly should avoid contact sports and seek immediate medical attention for trauma. If their platelet counts drop precipitously secondary to hypersplenism, they are at risk for both splenic rupture and intracranial bleeding.
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Contributor Information and Disclosures
Author

Lynne Ierardi-Curto, MD, PhD  Medical Geneticist, Laboratory Corporation of America (LabCorp), Northeast Division, Genetics Services

Disclosure: Nothing to disclose.

Specialty Editor Board

Edward Kaye, MD  Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, American Society of Gene Therapy, American Society of Human Genetics, Child Neurology Society, and Society for Inherited Metabolic Disorders

Disclosure: Genzyme Corporation Salary Management position

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Leonard G Feld, MD, PhD, MMM, FAAP  Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

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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