Medscape is available in 5 Language Editions – Choose your Edition here.


Lipid Storage Disorders Treatment & Management

  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Luis O Rohena, MD  more...
Updated: Oct 16, 2014

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.

Gaucher disease

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.[10]

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.

Glucosylceramide synthase inhibitors include miglustat (Zavesca) and eliglustat (Cerdelga). Miglustat was approved in 2003 as monotherapy for treatment of adults with mild-to-moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option.

Eliglustat was approved in August 2014 as first-line treatment for the long-term treatment of adults with Gaucher disease type 1. The dose of eliglustat is determined by establishing the patient’s CYP2D6 phenotype (ie, extensive metabolizers [EM], intermediate metabolizers [IM], or poor metabolizers [PM]).

Approval was based on efficacy data from 2 positive phase 3 studies involving 199 patients. One study involved patients new to therapy (trial 1), and the other involved patients switching from approved enzyme replacement therapies (trial 2). Efficacy data from 4 years of the Cerdelga phase 2 study also contributed to the approval. Improvements in study participants were observed in spleen size, platelet levels, hemoglobin levels, and liver volume, and noninferiority to enzyme replacement therapy (imiglucerase) was established in trial 2.[33]

Studies are currently underway to investigate the use of miglustat for the treatment of infantile-onset GM2 gangliosidosis and childhood Niemann-Pick type C.

Fabry disease

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.

Enzyme replacement therapy with recombinant alpha-galactosidase A (Replagal, TKT Corporation, Cambridge, Mass; Fabrazyme, Genzyme Corporation, Cambridge, Mass) is available. Fabrazyme is the only ERT for Fabry disease approved by the FDA.[10] 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.



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 sphingomyelinase deficiency (NPD type B) should have pulmonary consultations.



No specific dietary manipulations have an effect on the disease course. In particular, restriction of lipids is of no benefit.

Patients with sphingomyelinase deficiency (NPD) have elevated total cholesterol, although effects of dietary restriction of cholesterol have not been demonstrated.



Gaucher disease and patients with sphingomyelinase deficiency (NPD types A and B) 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.

Contributor Information and Disclosures

Lynne Ierardi-Curto, MD, PhD Attending Physician, Division of Metabolism, Children's Hospital of Philadelphia

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Eric T Rush, MD, FAAP, FACMG Clinical Geneticist, Munroe-Meyer Institute for Genetics and Rehabilitation; Assistant Professor of Pediatrics and Internal Medicine, University of Nebraska Medical Center

Eric T Rush, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American College of Physicians, Nebraska Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals<br/>Honoraria for: Alexion Pharmaceuticals and Biomarin Pharmaceuticals.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

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, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

  1. Jenkins RW, Canals D, Hannun YA. Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell Signal. 2009 Jun. 21(6):836-46. [Medline].

  2. Sasaki H, Arai H, Cocco MJ, White SH. pH dependence of sphingosine aggregation. Biophys J. 2009 Apr 8. 96(7):2727-33. [Medline]. [Full Text].

  3. Saini-Chohan HK, Mitchell RW, Vaz FM, Zelinski T, Hatch GM. Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders: Thematic Review Series: Genetics of Human Lipid Diseases. J Lipid Res. 2012 Jan. 53(1):4-27. [Medline]. [Full Text].

  4. 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].

  5. Ambrosio C, Serra S, Alexandre M, Malcata A. [Arthralgia, bone pain, positive antinuclear antibodies and thrombocytopenia...diagnosis: Niemann-Pick disease]. Acta Reumatol Port. 2009 Jan-Mar. 34(1):102-5. [Medline].

  6. [Guideline] Langlois S, Wilson RD. Carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. J Obstet Gynaecol Can. 2006 Apr. 28(4):324-43. [Medline]. [Full Text].

  7. Wasserstein M, Godbold J, McGovern MM. Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B. J Inherit Metab Dis. 2012 Jun 21. [Medline].

  8. Tsuboi K, Suzuki S, Nagai M. Descriptive epidemiology of Fabry disease among beneficiaries of the Specified Disease Treatment Research Program in Japan. J Epidemiol. 2012. 22(4):370-4. [Medline].

  9. Goldim MP, Garcia Cda S, de Castilhos CD, Daitx VV, Mezzalira J, Breier AC, et al. Screening of high-risk Gaucher disease patients in Brazil using miniaturized dried blood spots and leukocyte techniques. Gene. 2012 Oct 25. 508(2):197-8. [Medline].

  10. Aerts JM, Kallemeijn WW, Wegdam W, Joao Ferraz M, van Breemen MJ, Dekker N, et al. Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies. J Inherit Metab Dis. 2011 Jun. 34(3):605-19. [Medline]. [Full Text].

  11. Arora P, Tullu MS, Muranjan MN, et al. Congenital and inherited ophthalmologic abnormalities. Indian J Pediatr. 2003 Jul. 70(7):549-52. [Medline].

  12. Brunetti-Pierri N, Scaglia F. GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab. Aug 2008. 94(4):391-396. [Medline].

  13. Burton BK. Inborn errors of metabolism: the clinical diagnosis in early infancy. Pediatrics. 1987 Mar. 79(3):359-69. [Medline].

  14. Caciotti A, Donati MA, d'Azzo A, et al. The potential action of galactose as a "chemical chaperone": increase of beta galactosidase activity in fibroblasts from an adult GM1-gangliosidosis patient. Eur J Paediatr Neurol. Mar 2009. 13(2):160-164. [Medline].

  15. Dierks T, Schlotawa L, Frese MA, et al. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins. Biochim Biophys Acta. Apr 2009. 1793(4):710-725. [Medline].

  16. Galanaud D, Tourbah A, Lehericy S, et al. 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy. Mol Genet Metab. Feb 2009. 96(2):55-58. [Medline].

  17. Grabowski GA. Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet. Oct 2008. 372(9645):1263-1271. [Medline].

  18. Kooper AJ, Janssens PM, de Groot AN, et al. Lysosomal storage diseases in non-immune hydrops fetalis pregnancies. Clin Chim Acta. Sep 2006. 371(1-2):176-182. [Medline].

  19. Kraoua I, Sedel F, Caillaud C, Froissart R, Stirnemann J, Chaurand G, et al. A French experience of type 3 Gaucher disease: Phenotypic diversity and neurological outcome of 10 patients. Brain Dev. 2010 Mar 20. [Medline].

  20. Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, et al. Substrate reduction therapy in juvenile GM2 gangliosidosis. Mol Genet Metab. 2009 Sep-Oct. 98(1-2):215-24. [Medline].

  21. Maegawa GH, van Giersbergen PL, Yang S, et al. Pharmacokinetics, safety and tolerability of miglustat in the treatment of pediatric patients with GM2 gangliosidosis. Mol Genet Metab. Aug 2009. 97(4):284-291. [Medline].

  22. Mehta A, Clarke JT, Giugliani R, et al. Natural course of Fabry disease: changing pattern of causes of death in FOS - the Fabry Outcome Survey. J Med Genet. May 2009. Epub:[Medline].

  23. Mignot C, Gelot A, Bessieres B, et al. Perinatal-lethal gaucher disease. Am J Med Genet A. 2003. 120:338-344.

  24. Mistry PK, Smith SJ, Ali M, Hatton CS, McIntyre N, Cox TM. Genetic diagnosis of Gaucher's disease. Lancet. 1992 Apr 11. 339(8798):889-92. [Medline].

  25. Pastores GM, Giraldo P, Chérin P, Mehta A. Goal-oriented therapy with miglustat in Gaucher disease. Curr Med Res Opin. 2009 Jan. 25(1):23-37. [Medline].

  26. Pierson TM, Bonnemann CG, Finkel RS, Bunin N, Tennekoon GI. Umbilical cord blood transplantation for juvenile metachromatic leukodystrophy. Ann Neurol. 2008 Nov. 64(5):583-7. [Medline]. [Full Text].

  27. Ramsubir S, Nonaka T, Girbés CB, Carpentier S, Levade T, Medin JA. In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease. Mol Genet Metab. 2008 Nov. 95(3):133-41. [Medline]. [Full Text].

  28. Schneiderman J, Thormann K, charrow J, Kletzel M. Correction of enzyme levels with allogeneic hematopoietic progenitor cell transplantation in Niemann-Pick type B. Pediatr Blood Cancer. Dec 2007. 49(7):987-989. [Medline].

  29. Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. Oct 2007. 30(5):654-663. [Medline].

  30. Stein J, Garty BZ, Dror Y, et al. Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation. Eur J Pediatr. Jul 2007. 166(7):663-666. [Medline].

  31. Tolar J, Petryk A, Khan K, et al. Long-term metabolic, endocrine, and neuropsychological outcome of hematopoietic cell transplantation for Wolman disease. Bone Marrow Transplant. Jan 2009. 43(1):21-27. [Medline].

  32. Wraith JE, Vecchio D, Jacklin E, Abel L, Chadha-Boreham H, Luzy C, et al. Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial. Mol Genet Metab. 2010 Apr. 99(4):351-7. [Medline].

  33. Cerdelga (eliglustat) prescribing information [package insert]. IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland: Genzyme Ireland, Ltd. August 2014. Available at [Full Text].

Autosomal recessive inheritance pattern.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.