eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Lipid Storage Disorders: Differential Diagnoses & Workup

Author: Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Contributor Information and Disclosures

Updated: May 28, 2009

Differential Diagnoses

Gaucher Disease
Mucopolysaccharidosis Type IH

Workup

Laboratory Studies

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

Imaging Studies

  • Brain imaging
    • Brian 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 reticula-nodular infiltrates.
    • Findings are not associated with clinical pulmonary disease in young patients but can be accompanied by pulmonary dysfunction later in life.

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.
    • In addition, some disorders (eg, Gaucher disease) are possible to make genotype-phenotype correlations that predict disease severity and allow more precise genetic counseling. Thus, determination of genotype is recommended when possible.

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 and B 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.

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
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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].

  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. Burton BK. Inborn errors of metabolism: the clinical diagnosis in early infancy. Pediatrics. Mar 1987;DA - 19870331(3):359-69. [Medline].

  8. 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].

  9. Scriver CR, Beaudet AL, Sly WS. The Metabolic Basis of Inherited Disease. 1995.

  10. Watts W, Gibbs D. Lysosomal storage diseases: Biochemical and clinical aspects. 1986.

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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

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Contributor Information and Disclosures

Author

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

Medical Editor

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

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, 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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