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Low LDL Cholesterol (Hypobetalipoproteinemia) Workup

  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
 
Updated: Dec 16, 2014
 

Laboratory Studies

Laboratory studies include the following:

  • Routine complete blood cell count with differential, including platelet count - Some patients present with thrombocytopenia. In the absence of another obvious explanation, a low platelet count may be considered secondary to vitamin cofactor malabsorption, and one must consider the possibility of abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL).
  • Blood smear to assess erythrocyte morphology - Acanthocytosis (burr cells) may be evident in patients with FHBL, but even when the erythrocytes appear normal, an exceptionally low sedimentation rate can be demonstrated. Patients with ABL uniformly demonstrate acanthocytosis. From 40-80% of erythrocytes are acanthocytic. Mild to moderate anemia with mild to moderate reticulocytosis may also be present.
  • Basic chemistry (metabolic) panel - This test is used to exclude multisystem illness or evidence of malnutrition from another cause.
  • Liver function tests, including transaminases - Hepatic transaminases have been reported to be elevated in patients with ABL and FHBL. The mechanism for this finding is unclear.[20]
  • Stool studies - Search the stool for ova, parasites, and white blood cells in order to exclude other common causes of fat malabsorption.
  • Fasting lipid profile - A fasting lipid profile should be obtained from patients and their first-degree relatives, in the latter case to assist in distinguishing between ABL and homozygous FHBL. The parents of a patient with ABL have normal cholesterol levels, while the parents of a patient with homozygous FHBL have lower-than-average cholesterol levels.
    • Heterozygous FHBL - Patients with heterozygous FHBL may have total cholesterol levels that are below the fifth percentile (and may be less than 100 mg/dL). Plasma low-density lipoprotein (LDL) cholesterol levels are also reduced by one half or more. High-density lipoprotein (HDL) cholesterol levels are normal or slightly increased. Plasma triglyceride levels are reduced in some kindreds.
    • Homozygous FHBL - Patients with homozygous FHBL show extremely low plasma cholesterol and triglyceride levels.
    • ABL - Characteristically, extremely low levels of plasma cholesterol (< 50 mg/dL) and triglycerides are detected in infants and young children. Patients who are obligate heterozygotes have normal cholesterol levels.
  • ABL or homozygous FHBL diagnosis - This depends on finding acanthocytes in the peripheral blood and extremely low plasma levels of cholesterol (< 50 mg/dL). Chylomicrons (CMs) and very low-density lipoprotein (VLDL) are not detectable, and LDL is virtually absent.
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Imaging Studies

Imaging studies include the following:

  • Hepatic scan or ultrasonography to assess changes of fatty liver - Patients with liver enlargement, splenomegaly, or elevated levels of transaminases may need hepatic imaging studies to ascertain anatomy and function.
  • Magnetic resonance imaging (MRI) of the spinocerebellar region - This may become necessary in patients presenting with ataxic gait or vision loss.
  • Eye and retinal examination and imaging - An ophthalmic examination and retinal imaging may be needed in patients with visual disturbance and retinal degeneration.
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Other Tests

The molecular diagnosis of familial hypobetalipoproteinemia can be performed only in specialized laboratories; it is accomplished through the examination of the plasma apoB, using gel electrophoresis or deoxyribonucleic acid (DNA) analysis to identify specific mutations.

The demonstration of the molecular defect in persons with abetalipoproteinemia requires a specialized laboratory for the detection of low or absent MTP in intestinal biopsy specimens or DNA analysis to identify specific mutations.

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Procedures

Intestinal biopsy may be needed, along with electron microscopy.

  • The endoscopic appearance of the mucosa of the small intestine may be whitish, although this characteristic is usually limited to the villi.
  • The diagnosis is confirmed by the typical hematologic finding of acanthocytosis and the appearance of the small-bowel biopsy specimen, in which the tip enterocytes are filled with lipid droplets. The villi are normal but are lined with fat-containing enterocytes (engorged with triglycerides) that constitute the lipid droplets.
  • In specialized cases, light and transmission electron microscopy may show fat-loaded enterocytes (from marked triglyceride accumulation).

Liver biopsy is rarely needed but may become necessary to assess for fatty liver, chronic liver disease, or cirrhosis and to rule out other causes of hepatomegaly, fatty liver, and transaminase elevation.

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Histologic Findings

Intestinal biopsy reveals the gross appearance of white mucosa, usually limited to the villi. Histologically, the villi are normal but are lined with fat-containing enterocytes (engorged with triglycerides). In specialized cases, light and transmission electron microscopy may show fat-loaded enterocytes.

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Contributor Information and Disclosures
Author

Vibhuti N Singh, MD, MPH, FACC, FSCAI Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine; Director, Cardiology Division and Cardiac Catheterization Lab, Chair, Department of Medicine, Bayfront Medical Center, Bayfront Cardiovascular Associates; President, Suncoast Cardiovascular Research

Vibhuti N Singh, MD, MPH, FACC, FSCAI is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, American Medical Association, Florida Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

References
  1. Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014 Jun. 25(3):161-8. [Medline].

  2. Sen D, Dagdelen S, Erbas T. Hepatosteatosis with hypobetalipoproteinemia. J Natl Med Assoc. 2007 Mar. 99(3):284-6. [Medline].

  3. Hussain MM, Rava P, Pan X, et al. Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism. Curr Opin Lipidol. 2008 Jun. 19(3):277-84. [Medline].

  4. Young SG, Hubl ST, Smith RS, et al. Familial hypobetalipoproteinemia caused by a mutation in the apolipoprotein B gene that results in a truncated species of apolipoprotein B (B-31). A unique mutation that helps to define the portion of the apolipoprotein B molecule required for the format. J Clin Invest. 1990 Mar. 85(3):933-42. [Medline]. [Full Text].

  5. Linton MF, Farese RV, Young SG. Familial hypobetalipoproteinemia. J Lipid Res. 1993 Apr. 34(4):521-41. [Medline].

  6. Tarugi P, Averna M, Di Leo E, et al. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis. 2007 Dec. 195(2):e19-27. [Medline].

  7. Tarugi P, Averna M. Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum. Adv Clin Chem. 2011. 54:81-107. [Medline].

  8. Gutierrez-Cirlos C, Ordonez-Sanchez ML, Tusie-Luna MT, Patterson BW, Schonfeld G, Aguilar-Salinas CA. Familial hypobetalipoproteinemia in a hospital survey: genetics, metabolism and non-alcoholic fatty liver disease. Ann Hepatol. 2011 Apr-Jun. 10(2):155-64. [Medline].

  9. Herbert PN, Hyams JS, Bernier DN, et al. Apolipoprotein B-100 deficiency. Intestinal steatosis despite apolipoprotein B-48 synthesis. J Clin Invest. 1985 Aug. 76(2):403-12. [Medline]. [Full Text].

  10. Di Leo E, Lancellotti S, Penacchioni JY, et al. Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia. Atherosclerosis. 2005 Jun. 180(2):311-8. [Medline].

  11. Rader DJ, Brewer HB Jr. Abetalipoproteinemia. New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease. JAMA. 1993. 270:865-9. [Medline].

  12. Zamel R, Khan R, Pollex RL, et al. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis. 2008 Jul 8. 3:19. [Medline]. [Full Text].

  13. Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, et al. The role of the microsomal triglyceride transfer protein in abetalipoproteinemia. Annu Rev Nutr. 2000. 20:663-97. [Medline].

  14. Burnett JR, Zhong S, Jiang ZG, et al. Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia. J Biol Chem. 2007 Aug 17. 282(33):24270-83. [Medline]. [Full Text].

  15. Young SG, Bertics SJ, Curtiss LK, et al. Genetic analysis of a kindred with familial hypobetalipoproteinemia. Evidence for two separate gene defects: one associated with an abnormal apoB species, apolipoprotein B-37; and a second associated with low plasma concentrations of apoB-100. J Clin Invest. 1987 Jun. 79(6):1842-51. [Medline]. [Full Text].

  16. Martin-Morales R, Garcia-Diaz JD, Tarugi P, Gonzalez-Santos P, Saavedra-Vallejo P, Magnolo L, et al. Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene. Gene. 2013 Nov 15. 531(1):92-6. [Medline].

  17. Sankatsing RR, Fouchier SW, de Haan S, et al. Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol. 2005 Sep. 25(9):1979-84. [Medline]. [Full Text].

  18. Dieckert JP, White M, Christmann L, et al. Angioid streaks associated with abetalipoproteinemia. Ann Ophthalmol. 1989 May. 21(5):173-5, 179. [Medline].

  19. Dannoura AH, Berriot-Varoqueaux N, Amati P, et al. Anderson's disease: exclusion of apolipoprotein and intracellular lipid transport genes. Arterioscler Thromb Vasc Biol. 1999 Oct. 19(10):2494-508. [Medline]. [Full Text].

  20. Mehta NN, Desai HG. Persistent transaminase elevation due to heterozygous (familial) apolipoprotein B deficiency. Indian J Gastroenterol. 1997 Oct. 16(4):158-9. [Medline].

  21. Roussell MA, Hill AM, Gaugler TL, West SG, Vanden Heuvel JP, Alaupovic P, et al. Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins. Am J Clin Nutr. 2011 Dec 14. [Medline].

  22. Aguie GA, Rader DJ, Clavey V, et al. Lipoproteins containing apolipoprotein B isolated from patients with abetalipoproteinemia and homozygous hypobetalipoproteinemia: identification and characterization. Atherosclerosis. 1995 Dec. 118(2):183-91. [Medline].

  23. Collins DR, Knott TJ, Pease RJ, et al. Truncated variants of apolipoprotein B cause hypobetalipoproteinaemia. Nucleic Acids Res. 1988 Sep 12. 16(17):8361-75. [Medline]. [Full Text].

  24. Glueck CJ, Kelley W, Gupta A. Prospective 10-year evaluation of hypobetalipoproteinemia in a cohort of 772 firefighters and cross-sectional evaluation of hypocholesterolemia in 1,479 men in the National Health and Nutrition Examination Survey I. Metabolism. 1997 Jun. 46(6):625-33. [Medline].

  25. Goerg KJ, Borchard F, Luley C, et al. [Snow white small intestinal villi in hypobetalipoproteinemia]. Z Gastroenterol. 1996 Sep. 34(9):528-33. [Medline].

  26. Granot E, Deckelbaum RJ. Familial hypobetalipoproteinemia--differences in lipoprotein structure and composition. Ann Nutr Metab. 1993. 37(5):253-61. [Medline].

  27. Gregg RE, Wetterau JR. The molecular basis of abetalipoproteinemia. Curr Opin Lipidol. 1994 Apr. 5(2):81-6. [Medline].

  28. Hardman DA, Pullinger CR, Hamilton RL, et al. Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia. J Clin Invest. 1991 Nov. 88(5):1722-9. [Medline]. [Full Text].

  29. Humphries SE, Mailly F, Gudnason V, et al. The molecular genetics of pediatric lipid disorders: recent progress and future research directions. Pediatr Res. 1993 Oct. 34(4):403-15. [Medline].

  30. Ikewaki K, Nishiwaki M, Sakamoto T, et al. Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency. J Clin Invest. 1995 Sep. 96(3):1573-81. [Medline]. [Full Text].

  31. Kane JP, Havel RJ. Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins. Scriver C, Beaudet A, Sly W, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. 2717-52.

  32. Keidar S, Etzioni A, Brook JG, et al. Compound heterozygosity for abetalipoproteinaemia and familial hypobetalipoproteinaemia. J Med Genet. 1990 Feb. 27(2):133-4. [Medline]. [Full Text].

  33. Malloy MJ, Kane JP. Hypolipidemia. Med Clin North Am. 1982 Mar. 66(2):469-84. [Medline].

  34. Narchi H, Amr SS, Mathew PM, et al. Rickets as an unusual initial presentation of abetalipoproteinemia and hypobetalipoproteinemia. J Pediatr Endocrinol Metab. 2001 Mar. 14(3):329-33. [Medline].

  35. Pessah M, Beucler I, Loux N, et al. Genetic exclusion of apo-B gene in recessive abetalipoproteinemia. Biochem Biophys Res Commun. 1993 Jan 15. 190(1):97-103. [Medline].

  36. Raabe M, Kim E, Véniant M, et al. Using genetically engineered mice to understand apolipoprotein-B deficiency syndromes in humans. Proc Assoc Am Physicians. 1998 Nov-Dec. 110(6):521-30. [Medline].

  37. Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res. 2003 May. 44(5):878-83. [Medline]. [Full Text].

  38. Schonfeld G. The hypobetalipoproteinemias. Annu Rev Nutr. 1995. 15:23-34. [Medline].

  39. Schonfeld G, Lin X, Yue P. Familial hypobetalipoproteinemia: genetics and metabolism. Cell Mol Life Sci. 2005 Jun. 62(12):1372-8. [Medline].

  40. Shah SS, Desai HG. Apolipoprotein deficiency and chronic liver disease. J Assoc Physicians India. 2001 Feb. 49:274-8. [Medline].

  41. Tarugi P, Lonardo A, Ballarini G, et al. A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoprotein B (APO B-54.5). J Hepatol. 2000 Sep. 33(3):361-70. [Medline].

  42. Tarugi P, Lonardo A, Ballarini G, et al. Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. Gastroenterology. 1996 Oct. 111(4):1125-33. [Medline].

  43. Whitfield AJ, Barrett PH, Robertson K, et al. Liver dysfunction and steatosis in familial hypobetalipoproteinemia. Clin Chem. 2005 Jan. 51(1):266-9. [Medline]. [Full Text].

  44. Young SG. Recent progress in understanding apolipoprotein B. Circulation. 1990 Nov. 82(5):1574-94. [Medline].

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