eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Lipid Storage Disorders: Treatment & Medication
Updated: May 28, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
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.
- Enzyme replacement with recombinant acid a -glucosidase is available for the treatment of symptomatic patients with Gaucher disease type 1. Clinical trials have demonstrated that most extraskeletal symptoms are reversed within 12-36 months by an initial debulking dose of enzyme (60 IU/kg) administered by intravenous infusion every other week.
- The effectiveness of enzyme replacement in reversing and preventing bone manifestations is still under study; however, data indicate that early treatment may be efficacious in normalizing linear growth and bone morphology in affected children.
- Efforts are also underway to develop gene therapy for Gaucher disease type 1. 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.
- Alternative treatments are also being evaluated, including the use of agents designed to decrease the synthesis of glucosylceramide by chemical inhibition of glucosylceramide synthase.
- 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 α -galactosidase (Fabrazyme, Genzyme Corporation, Cambridge, MA; Replagal, TKT Corporation, Cambridge, MA) have revealed the safety and effectiveness of enzyme replacement therapy for Fabry disease at a dose of 1 mg/kg every other week. The enzyme replacement therapy is available in Europe and has been recently approved by the US Food and Drug Administration (FDA).
- At present, no specific treatment is available for Niemann-Pick disease (NPD). Orthotopic liver transplantation in an infant with type A disease and amniotic cell transplantation in several type B patients has been attempted with little or no success. Bone marrow transplantation in one patient with NPD type B was successful in reducing spleen and liver volumes, sphingomyelin content in the liver, number of NPD cells in marrow, and radiologic infiltration of lungs. However, no long-term information is available because patient died 3 months after transplantation. To date, lung transplantation has not been performed in any severely compromised patient with type B NPD. Future prospects for therapy include enzyme replacement and gene therapy.
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.
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.
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.
Medication
Enzyme replacement therapies
Specific enzymes are available to treat Gaucher and Fabry Disease.
Imiglucerase (Cerezyme)
A recombinant-derived analog of b -glucocerebrosidase. It is an enzyme used for replacement therapy in Gaucher disease. Catalyzes hydrolytic cleavage of glucocerebroside (a glycoprotein) to glucose and ceramide within the lysosomes of phagocytic cells in the reticuloendothelial system. This normally is a catabolic pathway of membrane lipids derived from hematologic cell turnover. A deficiency of this enzyme results in accumulation of glucocerebroside within tissue macrophages, which become engorged with the glycolipid. Treatment improves anemia and thrombocytopenia, reduces spleen and liver size, and decreases cachexia.
Adult
60 U/kg IV q2wk, typically; dose must be individualized and varies widely; initial dose may be as little as 2.5 U/kg 3 times/wk or as much as 60 U/kg q1-4wk
Dilute in 0.9% NaCl and infuse over 1-2 h
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May develop IgG antibodies (15%) and hypersensitivity (6-7%); may cause nausea, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia; may cause pruritus at site of injection
Agalsidase (Fabrazyme, Replagal)
Recombinant form of the human enzyme a -Gal A, levels of which are deficient in Fabry disease. Data from clinical trials show a decrease in GL-3 levels following enzyme replacement, reversal in lipid tissue storage, stabilized or improved renal and cardiac function, and reduced or relief from neuropathic pain. Following enzyme replacement, the long-term use of neuropathic pain medication has been reduced.
Agalsidase beta (Fabrazyme) is manufactured by Genzyme Corporation (Cambridge, Mass) and is based on expression of the human GLA gene in CHO cells.
Agalsidase alfa (Replagal) is manufactured by Transkaryotic Therapies, Inc (Cambridge, Mass) and is based on activation of the human GLA gene expression in human (skin) fibroblasts.
Adult
Initial dose:
Fabrazyme: 1 mg/kg IV infused over 4-6 h (initial infusion); subsequent infusions may be administered at a rate of 3-5 mg/min; repeat q2wk
Replagal: 0.2 mg/kg IV infused over 40 min q2wk
Maintenance dose: Not established
Pediatric
Not established; appropriate time to initiate treatment in children has not been determined
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause IgG antibody production (55% with Replagal; 83% with Fabrazyme); may cause allergic reactions (10% Replagal, 59% Fabrazyme), which are prevented by premedication with hydrocortisone and/or antihistamines (standard for Fabrazyme) before IV infusion; infusion-related events (ie, fever, rigors, hypertension) may be reduced or eliminated by slower rate of administration or interruption of treatment
More on Lipid Storage Disorders |
| Overview: Lipid Storage Disorders |
| Differential Diagnoses & Workup: Lipid Storage Disorders |
 Treatment & Medication: Lipid Storage Disorders |
| Follow-up: Lipid Storage Disorders |
| Multimedia: Lipid Storage Disorders |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Jenkins RW, Canals D, Hannun YA. Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell Signal. Jun 2009;21(6):836-46. [Medline].
Sasaki H, Arai H, Cocco MJ, White SH. pH dependence of sphingosine aggregation. Biophys J. Apr 8 2009;96(7):2727-33. [Medline].
Steczkowska M, Gergont A, Kroczka S, Nowak A. [Clinical features of GM1 and GM2 gangliosidosis in own observation]. Przegl Lek. 2008;65(11):819-23. [Medline].
Ambrosio C, Serra S, Alexandre M, Malcata A. [Arthralgia, bone pain, positive antinuclear antibodies and thrombocytopenia...diagnosis: Niemann-Pick disease]. Acta Reumatol Port. Jan-Mar 2009;34(1):102-5. [Medline].
[Guideline] Langlois S, Wilson RD. Carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. J Obstet Gynaecol Can. Apr 2006;28(4):324-43. [Medline]. [Full Text].
Arora P, Tullu MS, Muranjan MN, et al. Congenital and inherited ophthalmologic abnormalities. Indian J Pediatr. Jul 2003;70(7):549-52. [Medline].
Burton BK. Inborn errors of metabolism: the clinical diagnosis in early infancy. Pediatrics. Mar 1987;DA - 19870331(3):359-69. [Medline].
Mistry PK, Smith SJ, Ali M, Hatton CS, McIntyre N, Cox TM. Genetic diagnosis of Gaucher's disease. Lancet. Apr 11 1992;339(8798):889-92. [Medline].
Scriver CR, Beaudet AL, Sly WS. The Metabolic Basis of Inherited Disease. 1995.
Watts W, Gibbs D. Lysosomal storage diseases: Biochemical and clinical aspects. 1986.
Further Reading
- Relevant clinical guidelines include the following:
- Relevant clinical trials include the following:
- Related eMedicine topics
Keywords
lipid storage disorders, lipid storage diseases, gangliosidoses, glycolipidoses, sphingolipidoses, GM1 gangliosidoses, GM2 gangliosidoses, Gaucher disease, Gaucher's disease, Niemann-Pick disease, NPD, Fabry disease, Fabry's disease, fucosidosis, Schindler disease, Schindler's disease, metachromatic leukodystrophy, MLD, Krabbe disease, Krabbe's disease, multiple sulfatase deficiency, Farber disease, Farber's disease, Wolman disease, Wolman's disease, lipid storage disease, lipid-storage disease, lipid-storage disorders, lipid storage disorders, to thrive, relentless vomiting, abdominal distention, hepatosplenomegaly, treatment, diagnosis
