Genetics of Niemann-Pick Disease Workup

  • Author: Lynne Ierardi-Curto, MD, PhD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jan 12, 2010
 

Laboratory Studies

  • CBC count: Pancytopenia may be present secondary to the enlarged spleen in patients with Niemann-Pick disease (NPD).
  • Serum chemistry: Transaminase levels may be elevated.
  • Cholesterol: Reduced high-density lipoprotein (HDL-C) fraction is common in Niemann-Pick disease type B. In most patients this is accompanied by elevated total cholesterol and low density lipoprotein-cholesterol (LDL-C) levels.
  • Triglycerides: Most patients with Niemann-Pick disease type B and low serum HDL-C levels also have hypertriglyceridemia.
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Imaging Studies

  • Chest radiography reveals a typical reticulonodular pattern of infiltration, even in patients with no overt pulmonary symptoms. Calcified pulmonary nodules may be seen.
  • Bone age in patients with Niemann-Pick disease type B can lag as long as 2.5 years behind the chronologic age.
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Other Tests

  • Acid sphingomyelinase activity: The diagnosis of Niemann-Pick disease (NPD) is confirmed with measurement of enzyme activity in peripheral blood white cells or in cultured fibroblasts.
  • Acid sphingomyelinase mutation analysis: Targeted mutation analysis for 4 common SMPD1 mutations is available in clinical laboratories. Three common type A mutations (L302P, R496L, fsP330) predict the severe infantile form of the disease common in the Ashkenazi Jewish population. One common type B allele (deltaR608) is associated with the milder form of disease. Sequencing of the gene is available in clinical laboratories and permits identification of rare and private gene mutations. This information is useful for genotype-phenotype correlation. In addition, genotype information allows identification of carriers among at-risk family members and allows prenatal diagnosis using fetal DNA analysis.
  • Pulmonary function test: Testing typically reveals decreased oxygen diffusion, restrictive lung disease, and decreased maximal exercise tolerance.
  • Electrocardiogram (ECG) and stress test: Testing may be abnormal in patients with hyperlipidemia and evidence of coronary artery disease.
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Histologic Findings

  • The pathologic hallmark in Niemann-Pick disease types A and B is the histochemically characteristic lipid-laden foam cell, often termed the Niemann-Pick cell, on bone marrow examination.
  • These cells, which can be readily distinguished from Gaucher cells by histologic and histochemical characteristics, are not pathognomic for Niemann-Pick disease because histologically similar cells are found in patients with Wolman disease, cholesterol ester storage disease, lipoprotein lipase deficiency, and, in some patients, GM1 gangliosidosis type 2.
  • Bone marrow examination is not necessary for the diagnosis of Niemann-Pick disease.
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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

James Bowman, MD  Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists

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.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical 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.

References

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  3. 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].

  4. Cho YU, Chae JD, Lee WM, et al. [A Case of a Korean Adult Affected by Type B Niemann-Pick Disease: Secondary Sea-blue Histiocytosis and Molecular Characterization.]. Korean J Lab Med. Apr 2009;29(2):97-103. [Medline].

  5. Rodriguez-Pascau L, Gort L, Schuchman EH, Vilageliu L, Grinberg D, Chabas A. Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients. Hum Mutat. Mar 18 2009;[Medline].

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  7. Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH. The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations. Am J Hum Genet. Dec 2002;71(6):1413-9. [Medline].

  8. Bayever E, August CS, Kamani N, et al. Allogeneic bone marrow transplantation for Niemann-Pick disease (type IA). Bone Marrow Transplant. 1992;10 Suppl 1:85-6. [Medline].

  9. Fernandez-Burriel M, Pena L, Ramos JC, et al. The R608del mutation in the acid sphingomyelinase gene (SMPD1) is the most prevalent among patients from Gran Canaria Island with Niemann-Pick disease type B. Clin Genet. Mar 2003;63(3):235-6. [Medline].

  10. Hellani A, Schuchman EH, Al-Odaib A, et al. Preimplantation genetic diagnosis for Niemann-Pick disease type B. Prenat Diagn. Dec 15 2004;24(12):943-8. [Medline].

  11. McGovern MM, Aron A, Brodie SE, Desnick RJ, Wasserstein MP. Natural history of type A Niemann-pPck disease; Possible endpoints for therapeutic trials. Neurology. Jan 24/2006;66(2):228-232. [Medline].

  12. McGovern MM, Wasserstein MP, Giugliani R, et al. A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. Pediatrics. Aug 2008;122(2):e341-9. [Medline].

  13. Mendelson DS, Wasserstein MP, Desnick RJ, Glass R, Simpson W, Skloot G, et al. Type b niemann-pick disease: findings at chest radiography, thin-section CT, and pulmonary function testing. Radiology. Nov 22/2006;238(1):339-345. [Medline].

  14. Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. Oct 2007;30(5):654-63. [Medline].

  15. Shah AJ, Kapoor N, Crooks GM, et al. Successful hematopoietic stem cell transplantation for Niemann-Pick disease type B. Pediatrics. Oct 2005;116(4):1022-5. [Medline].

  16. Takahashi T, Suchi M, Desnick RJ, et al. Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms. J Biol Chem. Jun 25 1992;267(18):12552-8. [Medline].

 
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Autosomal recessive inheritance pattern.
 
 
 
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