eMedicine Specialties > Endocrinology > Metabolic Disorders

Low LDL Cholesterol (Hypobetalipoproteinemia): Follow-up

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

Follow-up

Further Inpatient Care

  • Infants who present with failure to thrive may require additional monitoring and therapy in the hospital. This therapy may include the following:
    • Parenteral vitamin supplementation
    • Electrolyte and nutrient supplementation
  • Patients with spinocerebellar degeneration and severe gait disturbances may need supportive measures. They may also need orthotic appliances.
  • Visual assessment and therapy are indicated for retinal degeneration.

Further Outpatient Care

  • Diet low in long-chain fatty acids
  • Antidiarrheal medication as needed
  • High-dose fat-soluble vitamin supplementation, particularly vitamin E

Inpatient & Outpatient Medications

Transfer

  • Transfer is rarely required for patients who are finally identified as having abetalipoproteinemia (ABL) or familial hypobetalipoproteinemia (FHBL).
  • Patients with advanced spinocerebellar degeneration who are unable to walk may occasionally require transfer to a tertiary care facility. Any safe method of transfer is adequate for these patients.

Deterrence/Prevention

  • Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are inherited disorders caused by genetic mutations.
  • Obligate heterozygotes (ie, parents or offspring of homozygote patients) and possible heterozygotes (ie, siblings) should be informed that if their spouse has a very low plasma cholesterol level, the possibility exists that their children could have homozygous or compound heterozygous hypobetalipoproteinemia. Such persons should be referred to a genetic counselor at a lipid clinic.4

Complications

  • Gastrointestinal
    • Steatorrhea
    • Malabsorption of fat-soluble vitamins (ie, vitamins A, D, E, and/or K)
    • Steatorrhea-induced calcium malabsorption (may lead to rickets)
  • Ophthalmologic
    • Ophthalmoplegia
    • Retinal degeneration
  • Neurologic - Spinocellular degeneration
  • Hematologic - Acanthocytosis

Prognosis

  • Prognosis is reasonably good for most patients who are diagnosed early.
  • Patients with prolonged vitamin deficiency, especially of vitamin E, may develop very limiting ataxia and gait disturbances.
  • Some patients may develop retinal degeneration and blindness.

Patient Education

  • Educating patients about the implications of their disease is of paramount importance. They should be counseled about the possible long-term complications, including blindness and gait disturbances. The need for periodic monitoring should be emphasized.
  • Genetic counseling is needed for patients and their first-degree relatives.4
  • Nutritional counseling should include dietary recommendations for a low-fat diet (low in long-chain fatty acids) and advice to take prescribed vitamins as directed.
  • For excellent patient education resources, visit eMedicine's Cholesterol Center. Also, see the eMedicine's patient education articles Cholesterol and Children and Understanding Your Cholesterol Level.

Miscellaneous

Medicolegal Pitfalls

  • The diagnosis of abetalipoproteinemia (ABL) or familial hypobetalipoproteinemia (FHBL) must be considered in infants and children presenting with malabsorption syndromes. Failure to recognize the syndrome may result in long-term vitamin E deficiency and neurologic sequelae, which may have legal consequences for the health care providers.

Special Concerns

  • Genetic issues pertaining to abetalipoproteinemia (ABL) or familial hypobetalipoproteinemia (FHBL) should be addressed with patients and their first-degree relatives.
 


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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