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Low LDL Cholesterol (Hypobetalipoproteinemia): Treatment & Medication

Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI, Director, Suncoast Cardiovascular Center; Chair, Cardiology Division and Cath Labs, Department of Medicine, Bayfront Medical Center; Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine
Coauthor(s): Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Contributor Information and Disclosures

Updated: Aug 4, 2009

Treatment

Medical Care

Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are rare genetic disorders. Infants and children who present with homozygous FHBL or ABL require early treatment with very high doses of vitamin E. Management in adults includes treatment of the complications of the disorders.

To prevent the neurologic manifestations that occasionally occur with FHBL, heterozygous patients receive modest supplementation with vitamin E.

  • Dietary manipulation4
    • Severe restriction of long-chain fatty acids to 15 g per day is recommended to improve the complications of fat malabsorption.
    • In infants with failure to thrive, brief supplementation with medium-chain triglycerides may be necessary, but the amount must be closely monitored to avoid liver toxicity.
  • Vitamin supplementation4
    • Very large doses of oral vitamin E (100-300 mg/kg/d) are used to raise the tissue vitamin E concentration and to prevent neurologic complications in homozygotes.
    • Heterozygotes with FHBL should receive modest doses of vitamin E to prevent the development of neurologic complications.
    • Vitamin A (10,000-25,000 IU/d) supplementation is instituted if an elevated prothrombin time suggests vitamin K depletion.
  • Symptomatic treatment and treatment of complications

Consultations

Patients who present with advanced complications of abetalipoproteinemia (ABL) or familial hypobetalipoproteinemia (FHBL), as well as the patients' first-degree relatives, require a comprehensive evaluation for the diagnosis and management of these conditions and for genetic counseling.4 Expertise from the following consultants may be needed:

  • Lipidologist - Patients with ABL or FHBL may require an extensive and time-consuming assessment, including genetic studies and chromosomal analyses. A lipidologist at a major center specializing in the disorders of lipid metabolism is the most appropriate consultant to involve from the start.
  • Gastroenterologist - In patients with malabsorption syndrome, a thorough assessment by a gastroenterologist is necessary to exclude the many other common causes of this condition.
  • Hepatologist - Patients presenting with transaminase elevation and hepatic enlargement may require specialized evaluation by a liver specialist.
  • Ophthalmologist - Patients require assessment of any visual disturbance by an ophthalmologist. They also may need monitoring and periodic follow-up assessments for the development of retinal degeneration.
  • Neurologist - A complete neurologic evaluation is necessary in each patient. Patients, particularly those who present with gait disturbances or ataxia, need a thorough evaluation and subsequent monitoring of any spinocerebellar degeneration.
  • Nutritionist - A nutritionist must carefully evaluate the diets of patients with ABL or FHBL and suggest appropriate modifications.

Diet

  • A low-fat diet, especially a reduction in the intake of long-chain fatty acids to less than 15 g per day, may alleviate intestinal symptoms.
  • Oral supplementation of fat-soluble vitamins (ie, A, D, E, K) is needed.
  • Supplementation of vitamin E (alpha tocopherol in high doses) may prevent progression and may even reverse some of the stigmata of spinocerebellar degeneration. However, no randomized or case-controlled study is available to support this intervention.

Activity

  • No particular restriction in activity is recommended. Patients should be as active as dictated by their general health.
  • In patients with spinocerebellar degeneration or ataxia, only well-tolerated and supervised activity should be advised. Such patients may benefit from orthotic devices.

Medication

Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) have no specific medical therapy other than vitamin supplementation, particularly high doses of vitamin E. Symptomatic medications for diarrhea and treatment of the cause of malabsorption may be needed. Dietary treatment related to ABL and FHBL is quite rigorous.

Vitamins

High-dose vitamin E therapy is used to raise tissue levels of tocopherol and to prevent the development of neurologic sequelae.


Alpha tocopherol, vitamin E (Vita-Plus E Softgels, Vitec, Aquasol E)

Vitamin E protects polyunsaturated fatty acids in membranes from attack by free radicals and protects red blood cells against hemolysis.

Adult

100-300 mg/kg/d PO in divided doses
Heterozygous FHBL: 400-800 mg/d

Pediatric

Not established but should be strongly considered

Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Large doses may induce vitamin K deficiency or necrotizing enterocolitis


Vitamin A (Del-Vi-A, Palmitate-A 5000)

Cofactor in many biochemical processes.

Adult

10,000-25,000 IU/d PO

Pediatric

Not established

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

X - Contraindicated; benefit does not outweigh risk

Precautions

Monitor for toxicity if dose >25,000 U/d

More on Low LDL Cholesterol (Hypobetalipoproteinemia)

Overview: Low LDL Cholesterol (Hypobetalipoproteinemia)
Differential Diagnoses & Workup: Low LDL Cholesterol (Hypobetalipoproteinemia)
Treatment & Medication: Low LDL Cholesterol (Hypobetalipoproteinemia)
Follow-up: Low LDL Cholesterol (Hypobetalipoproteinemia)
References
Further Reading
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References

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

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

  3. 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. Mar 1990;85(3):933-42. [Medline]. [Full Text].

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

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

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

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

  8. 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].

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

  10. 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].

  11. 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. Aug 17 2007;282(33):24270-83. [Medline]. [Full Text].

  12. 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. Jun 1987;79(6):1842-51. [Medline]. [Full Text].

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

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

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

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

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

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

  19. 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. Jun 1997;46(6):625-33. [Medline].

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

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

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

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

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

  25. 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. Sep 1995;96(3):1573-81. [Medline]. [Full Text].

  26. Kane JP, Havel RJ. Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins. In: 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.

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

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

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

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

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

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

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

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

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

  36. 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. Sep 2000;33(3):361-70. [Medline].

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

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

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

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Keywords

low LDL cholesterol, cholesterol, LDL, LDL cholesterol, ABL, abetalipoproteinemia, hypobetalipoproteinemia, cholesterol levels, good cholesterol, triglyceride, triglycerides, lipoprotein, lipoproteins, apolipoprotein, Bassen-Kornzweig syndrome, HBL, familial hypobetalipoproteinemia, FHBL, FH-beta, low low-density lipoprotein cholesterol, Anderson disease, Anderson's disease

chylomicron retention disease, chylomicron-retention disease, lipoprotein metabolism dysfunction, lipoprotein metabolism disorder, fat malabsorption, spinocerebellar degeneration, acanthocytosis, acanthocytic red blood cells, pigmented retinopathy, malabsorption syndrome, vitamin E deficiency, vitamin deficiency, failure to thrive, ataxia, steatorrhea, retinal degeneration, blindness, spinocellular degeneration, retinitis pigmentosa

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Contributor Information and Disclosures

Author

Vibhuti N Singh, MD, MPH, FACC, FSCAI, Director, Suncoast Cardiovascular Center; Chair, Cardiology Division and Cath Labs, Department of Medicine, Bayfront Medical Center; Clinical Assistant Professor, Division of Cardiology, University of South Florida College of Medicine
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, and Florida Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Udaya M Kabadi, MD, Professor, Department of Medicine, University of Iowa College of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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 Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor 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, 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, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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