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Low LDL Cholesterol (Hypobetalipoproteinemia) Clinical Presentation

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


The phenotypic expression of homozygous abetalipoproteinemia (ABL) is essentially the same as that for homozygous familial hypobetalipoproteinemia (FHBL). Chylomicrons (CMs), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) are essentially absent. Severe fat malabsorption and all of the sequelae of that condition are present during infancy and beyond. ABL, if left untreated, can result in early mortality.

A study by Sankatsing and colleagues of patients with FHBL evaluated (a) the arterial wall stiffness and carotid intima-media thickness (IMT), measured by B-mode ultrasonography, as noninvasive, surrogate markers for cardiovascular disease (CVD), and (b) the presence and severity of hepatic steatosis, as assessed by abdominal ultrasonography.[17] The hepatic transaminase levels were found to be only modestly elevated, although the prevalence (54% vs 29%; P = 0.01) and severity of steatosis were significantly higher in individuals with FHBL than they were in controls. Furthermore, despite similar IMT measurements, arterial stiffness was significantly lower in patients with FHBL (P = 0.04) than it was in controls, suggesting cardiovascular protection.

Heterozygotes with the mutation that leads to either ABL or FHBL are generally asymptomatic. However, because FHBL is a codominant condition (unlike ABL, which is a recessive disorder), carriers have half the normal levels of beta lipoproteins. Cholesterol levels range from 40-180 mg/dL. Some carriers may present with signs and symptoms of neurologic involvement.

  • Failure to thrive in infancy
    • Homozygous ABL and homozygous FHBL are associated with severe fat malabsorption from birth.
    • Children fail to thrive during first year of life.
  • Gastroenterologic symptoms
    • Steatorrhea and diarrhea are present.
    • Stools are pale, malodorous, and bulky.
    • The abdomen may be distended.
    • In patients older than 10 years, intestinal symptoms tend to be less severe, probably due, in part, to the learned avoidance of high fat intake.
  • Neurologic symptoms
    • Intellectual development tends to be slow.
    • Deep tendon reflexes are absent.
    • Patients develop peripheral neuropathy.
    • Loss of position and vibration sense occurs.
    • Intention tremors develop.
  • Ophthalmologic symptoms
    • Retinitis pigmentosa occurs in adolescents.
    • Symptoms begin with decreased night and color vision.
    • Daytime visual acuity gradually deteriorates.
    • Virtual blindness occurs by the fourth decade of life.


The physical examination usually reveals fat malabsorption stigmata, spinocerebellar tract involvement, and ocular involvement. Some of the signs encountered due to fat malabsorption may include the following:

  • Gastroenterologic - Patients may have abdominal distension.
  • Neurologic
    • The first sign of disease is usually the loss of deep tendon reflexes.
    • Next, distal lower extremity vibratory and proprioceptive senses decrease.
    • Cerebellar signs, such as dysmetria, ataxia, and spastic gait, then ensue.
    • Finally, patients develop extensor plantar responses.
  • Ophthalmologic
    • Patients develop angioid streaks and retinal degeneration (or retinitis pigmentosa).[18]
    • Ophthalmoplegia is also reported.
  • Hepatic - Patients may have an enlarged, fatty liver with signs of chronic liver disease (eg, cirrhosis).


Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are caused by genetic defects that encode for MTP or apoB molecules, respectively.

  • ABL is caused by mutations in the MTP gene.
  • FHBL is caused by a mutation in the APOB gene.
  • Secondary hypobetalipoproteinemia may be associated with cancers, liver disease, severe malnutrition, and other wasting disorders.
Contributor Information and Disclosures

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.

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