Lipid Storage Disorders Workup

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

Laboratory Studies

Diagnosis of lipid storage disorders depends on demonstration of specific enzymatic deficiency in peripheral blood leukocytes or cultured fibroblasts.

Next

Imaging Studies

  • Brain imaging
    • Brain imaging studies are frequently obtained during evaluation of infants and children with developmental delay or retrogression. However, they are not essential to diagnosis, which depends on demonstration of specific enzymatic deficiency in peripheral blood leukocytes or cultured fibroblasts.
    • Findings vary with different disorders.
  • Skeletal radiographs
    • In GM1 gangliosidosis, skeletal abnormalities are similar to those associated with mucopolysaccharidoses. They include anterior beaking of vertebrae, enlargement of sella-turcica and thickening of calvaria.
    • In Gaucher disease type 1, more than half of patients have radiological evidence of skeletal involvement including an Erlenmeyer flask deformity of the distal femur.
    • In patients with symptomatic bone disease, lytic lesions can develop in long bones like the femur, ribs, and pelvis. Osteosclerosis may be evident at an early age.
  • Chest radiograph
    • Patients with Niemann-Pick disease (NPD) typically have fine reticular-nodular infiltrates.
    • Findings are not associated with clinical pulmonary disease in young patients but can be accompanied by pulmonary dysfunction later in life.
  • Abdominal radiograph: Patients with Wolman disease typically have calcification of the adrenal noted on abdominal radiograph.
Previous
Next

Other Tests

Genetic testing

  • For most disorders, carrier identification and prenatal diagnosis are available. Making a specific diagnosis in an affected child is important in order to provide genetic counseling.
  • More recently, investigators have focused efforts on determining molecular basis. These studies have resulted in identification of specific disease-causing mutations, allowing for improved diagnosis, prenatal diagnosis and carrier identification.
  • For some disorders (eg, Gaucher disease), it is possible to make genotype-phenotype correlations that predict disease severity and allow more precise genetic counseling. Thus, determination of genotype is recommended when possible.
Previous
Next

Histologic Findings

  • Examination of tissues reveals pathologic storage of substrate in many tissues including liver, bone marrow and, for some disorders, the brain.
  • Gaucher disease has a pathologic hallmark, which is the Gaucher cell in the reticuloendothelial system, particularly in bone marrow. Cells, which are 20-100 µm in diameter, have a wrinkled-paper appearance resulting from presence of intracytoplasmic inclusions of substrate. Cytoplasm reacts strongly positive with periodic acid-Schiff stain. Presence in bone marrow and organ tissue specimens is highly suggestive of Gaucher disease, although it can be found in patients with granulocytic leukemia and myeloma.
  • NPD types A, B, and C have a pathological hallmark, which is histochemically lipid-laden foam cells, often called Niemann-Pick cells.[4] These cells can be readily distinguished from Gaucher cells by their histologic and histochemical characteristics. They are not pathognomonic for NPD because histologically similar cells are found in patients with Wolman disease, cholesterol ester storage disease, lipoprotein lipase deficiency, and GM1 gangliosidosis type 2.
Previous
Proceed to Treatment & Management
 
 
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.

References

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

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

  3. 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].

  4. 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].

  5. [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].

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

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

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

  9. 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].

  10. 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].

  11. 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].

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

  13. 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].

  14. 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].

  15. 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].

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

  17. 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].

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

  19. 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. Nov 2008;95(3):133-41. [Medline]. [Full Text].

  20. 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].

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

  22. 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].

  23. 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].

  24. 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. Mar 20 2010;[Medline].

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

  26. 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. Apr 2010;99(4):351-7. [Medline].

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

 
Previous
Next
 
Autosomal recessive inheritance pattern.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.