eMedicine Specialties > Endocrinology > Metabolic Disorders

Lecithin-Cholesterol Acyltransferase Deficiency: Differential Diagnoses & Workup

Author: Vasudevan A Raghavan, MBBS, MD, MRCP, Assistant Professor, Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, Ohio State University
Coauthor(s): Weerapan Khovidhunkit, MD, PhD, Clinical Instructor, Department of Medicine, Division of Endocrinology and Metabolism, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thailand
Contributor Information and Disclosures

Updated: Sep 18, 2007

Differential Diagnoses

Hypercholesterolemia, Familial
Hypercholesterolemia, Polygenic
Hypertriglyceridemia

Other Problems to Be Considered

Apolipoprotein (apo)A-I/apoC-III/apoA-IV deficiency
apoA-I deficiency
Combined apoA-I/apoC-III deficiency
Familial dyslipidemia
Familial hypoalphalipoproteinemia
Tangier disease

Workup

Laboratory Studies

  • Familial LCAT deficiency
    • CBC count: Normochromic normocytic anemia with anisopoikilocytosis, target cells, stomatocytes, and hematological evidence of hemolysis may be present.
    • Urinalysis: Proteinuria is commonly detected during the second or third decade of life. Less common findings include hyaline and granular casts and red blood cells.
    • In some patients, laboratory evidence of progressive renal insufficiency, such as increased plasma BUN, increased plasma creatinine, and decreased creatinine clearance
    • Low concentrations of HDL cholesterol (generally <10 mg/dL)
    • High concentrations of plasma unesterified (free) cholesterol
    • Low concentrations of plasma cholesterol ester
    • Elevated very low-density lipoprotein and triglyceride levels
    • Negligible plasma LCAT activity: Plasma fails to esterify radioactive cholesterol in exogenous apo A-I–containing liposomes.
    • Negligible plasma cholesterol esterification rate: Plasma fails to esterify radioactive cholesterol in endogenous lipoproteins.
  • Fish eye disease
    • No anemia upon CBC count
    • No proteinuria upon urinalysis
    • No laboratory evidence of renal insufficiency
    • Low concentrations (10% of normal) of HDL cholesterol
    • High concentrations of unesterified (free) cholesterol in HDL
    • Low concentrations of cholesterol ester in HDL, but normal in very low-density lipoprotein and low-density lipoprotein
    • Elevated very low-density lipoprotein and triglyceride levels
    • Negligible LCAT activity in HDL
    • Normal plasma cholesterol esterification rate
    • Failure of plasma to esterify radioactive cholesterol in exogenous lipoproteins or HDL, but not in low-density lipoprotein

Imaging Studies

Imaging is not beneficial in diagnosis.

Other Tests

A definitive diagnosis requires mutational analysis of the LCAT gene and a functional analysis of the mutated gene product.

Histologic Findings

Foam cells are found in the biopsy specimens from the bone marrow, kidneys, and spleen. Sea-blue histiocytes by Giemsa staining are found in the bone marrow and spleen. Postmortem studies showed atherosclerotic changes of the aorta and arteries in some patients with familial LCAT deficiency and fish eye disease.

More on Lecithin-Cholesterol Acyltransferase Deficiency

Overview: Lecithin-Cholesterol Acyltransferase Deficiency
Differential Diagnoses & Workup: Lecithin-Cholesterol Acyltransferase Deficiency
Treatment & Medication: Lecithin-Cholesterol Acyltransferase Deficiency
Follow-up: Lecithin-Cholesterol Acyltransferase Deficiency
References
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References

  1. Bérard AM, Clerc M, Brewer B, Santamarina-Fojo S. A normal rate of cellular cholesterol removal can be mediated by plasma from a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency. Clin Chim Acta. Dec 2001;314(1-2):131-9. [Medline].

  2. Elkhalil L, Majd Z, Bakir R, et al. Fish-eye disease: structural and in vivo metabolic abnormalities of high-density lipoproteins. Metabolism. May 1997;46(5):474-83. [Medline].

  3. Hirano K, Kachi S, Ushida C, Naito M. Corneal and macular manifestations in a case of deficient lecithin: cholesterol acyltransferase. Jpn J Ophthalmol. Jan-Feb 2004;48(1):82-4. [Medline].

  4. Kuivenhoven JA, Pritchard H, Hill J, et al. The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. J Lipid Res. Feb 1997;38(2):191-205. [Medline].

  5. Mertens A, Verhamme P, Bielicki JK, et al. Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice: LCAT gene transfer decreases atherosclerosis. Circulation. Apr 1 2003;107(12):1640-6. [Medline].

  6. Pritchard PH, Hill JS. Genetic disorders of lecithin:cholesterol acyltransferase. In: Betterridge J, Illingworth R, Sheperd J, eds. Lipoproteins in Health and Disease. 799-814. ed. London, England: Hodder and Stoughton; 1999:799-814.

  7. Santamarina-Fojo S, Hoef J, Assmann G. Lecithin: cholesterol acyltransferase deficiency and fish-eye disease. In: Wonsiewicz M, Noujaim S, Boyle P, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001:2817-33.

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Further Reading

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Keywords

LCAT deficiency, familial lecithin-cholesterol acyltransferase deficiency, familial LCAT deficiency, cholesterol acyltransferase deficiency, fish-eye disease, fish eye disease, high-density lipoprotein, HDL, low-density lipoprotein, LDL, atherosclerosis, renal failure, kidney failure, corneal opacities, visual impairment, hypoalphalipoproteinemia, opaque cornea, corneal opacity, progressive corneal opacification

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Contributor Information and Disclosures

Author

Vasudevan A Raghavan, MBBS, MD, MRCP, Assistant Professor, Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, Ohio State University
Vasudevan A Raghavan, MBBS, MD, MRCP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, Endocrine Society, National Lipid Association, and Royal College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Weerapan Khovidhunkit, MD, PhD, Clinical Instructor, Department of Medicine, Division of Endocrinology and Metabolism, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thailand
Weerapan Khovidhunkit, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

David M Klachko, MBBCh, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri
David M Klachko, MBBCh is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Missouri State Medical Association, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kent Wehmeier, MD, Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine
Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

 
 
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