Abetalipoproteinemia

What is Abetalipoproteinemia (MTP Deficiency)?

Abetalipoproteinemia (ABL) is a very rare, inherited, autosomal recessive disorder with a prevalence of less than one in a million. ABL is caused by a mutation in the MTTP gene which codes for microsomal triglyceride protein (MTP). Abnormal MTP function leads to compromised absorption and transportation of fat (and fat-soluble vitamins) in the intestine and the liver. Therefore, individuals with ABL typically have very low blood cholesterol, particularly LDL-cholesterol (LDL-C), and VLDL cholesterol (VLDL-C). This leads to malnutrition, nervous system problems, and abnormal red blood cells count.  1

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What are the symptoms of Abetalipoproteinemia (ABL)?

Symptoms of ABL typically develop in infancy after breastfeeding. Early symptoms can include:   2,3

  • Fatty diarrhea
  • Vomiting
  • Failure to thrive
  • Abnormal red blood cells and anemia

Late symptoms can include:  2,3

  • Muscle weakness
  • Numbness in hands and feet (Peripheral neuropathy)
  • Vision problems
  • Fatty liver and liver enlargement
  • Bleeding disorder


How is Abetalipoproteinemia (ABL) diagnosed?

Currently, there is no formal diagnostic criteria for ABL. ABL is suspected in infants who have symptoms as described above. Supportive blood tests findings are usually obtained. Genetic testing is confirmative after basic laboratory tests.  4 Blood tests:   2

  • Complete blood count
  • Coagulation test
  • Cholesterol level (including Apolipoprotein B (ApoB) level)
  • Fat-soluble vitamin (Vitamin A, D, E, and K) levels
  • Liver function test

Genetic testing to confirm the mutation of MTTP gene: Genetic testing through a lab that specializes in lipid testing can help assess the severity of the disorder.  5 Additional tests are sometimes obtained in search for affected organs:  This includes liver ultrasound, bone density test, eye examination, heart ultrasound (echocardiogram), and nerve function test (electromyography).  1

What initial medical care is needed for individuals with ABL?

Specialty consultation for multidisciplinary evaluation:  1

  • Lipidologist
  • Gastroenterologist and hepatologist
  • Neurologist
  • Ophthalmologist
  • Hematologist
  • Dietitian
  • Physical therapist and occupational therapist
  • Genetic counsellor for patients and their first-degree relatives

Dietary modification is the standard of care for individuals with ABL: Gastrointestinal symptoms can be prevented by fat intake restriction. Supplement nutrient is also recommended to maintain normal growth and development.  4 Further details of dietary modification can be found in treatment options section.  2

What ongoing medical care is recommended for individuals with ABL?

Periodical evaluation is required to ensure normal growth and development. Additionally, routine tests are recommended to monitor for damage to other organs.  6 At every visit:   2,4

  • Routine physical examination
  • Evaluation of growth and development for children and adolescents

Every 6 months – 1 year:  2, 4

  • Laboratory testing:
  • Complete blood count, reticulocyte count, and sedimentation rate
  • Coagulation test
  • Liver function test
  • Essential vitamin levels: Vitamin A, beta-carotene, vitamin D, vitamin E, vitamin K, vitamin B12, and folic acid levels
  • Iron panel
  • Thyroid hormone level
  • Eye examination
  • Neurological examination

Every 3 years:  6,7

  • Liver ultrasound
  • Heart ultrasound (echocardiography)
  • Bone density test

In adolescents and young adults, physical and occupational therapy are often involved to alleviate muscle weakness and neurological difficulties.  2

What are the treatment options for individuals with ABL?

  1. Multidisciplinary care is the key to management for ABL patients. Treatment involves addressing specific symptoms of each patient. This requires combined efforts of a team of specialists, including ophthalmologist, neurologist, hepatologist, and lipidologist.  1
  2. Reduction of dietary fat intake helps prevent diarrhea. However, the patient should receive adequate calorie intake to avoid delayed growth.  2
  3. Usually, essential fatty acid supplement is given to the patients to prevent malnutrition. Medium-chain triglyceride is sometimes administered in infants if necessary. Neurological and eye examination in addition to blood tests are used as guidance for fatty acid and triglyceride supplementation.  2,7
  4. Vitamin supplementation is typically recommended especially in individuals with vitamin deficiency. Supplements may include vitamin A, D, E, and K. In patients with anemia, iron, folate, and vitamin B 12 are frequently given.  2,7
  5. Exercise recommendations by physical, and occupational therapists, as well as speech therapy are essential for maintaining physical function in adolescents with neurological symptoms.  2
  6. As gene therapy technology has been rapidly progressed in the past decade, gene transfer may be available in the future.  8


To find a lipid specialist in your area, use the  “find a clinician” tool on learnyourlipids.com.

References 

  1. Junaid SZS, Patel K. Abetalipoproteinemia. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
  2. Takahashi, Manabu et al. “Current Diagnosis and Management of Abetalipoproteinemia.” Journal of atherosclerosis and thrombosis vol. 28,10 (2021): 1009-1019. doi:10.5551/jat.RV17056
  3. Davidson M.H. Toth P.P. Maki K.C. Therapeutic Lipidology. Contemporary Cardiology. Humana, Cham 202 https://doi.org/10.1007/978-3-030-56514-5_34
  4. Bredefeld, Cindy et al. “New Classification and Management of Abetalipoproteinemia and Related Disorders.” Gastroenterology vol. 160,6 (2021): 1912-1916. doi:10.1053/j.gastro.2020.11.040
  5. Véronique Pons, Corinne Rolland, Michel Nauze, Marie Danjoux, Gérald Gaibelet, Anne Durandy, Agnès Sassolas, Emile Lévy, François Tercé, Xavier Collet, Emmanuel Mas. A severe form of abetalipoproteinemia caused by new splicing mutations of microsomal triglyceride transfer protein (MTTP). Human Mutation. March 10, 2011. https://doi.org/10.1002/humu.21494 Accessed 2/4/2024
  6. Welty, Francine K. “Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.” Current opinion in lipidology vol. 31,2 (2020): 49-55. doi:10.1097/MOL.0000000000000663
  7. Burnett, John R, et al. “Abetalipoproteinemia.” GeneReviews®, edited by Margaret P Adam et. al., University of Washington, Seattle, 25 October 2018.
  8. Kassim SH, Wilson JM, Rader DJ. Gene therapy for dyslipidemia: a review of gene replacement and gene inhibition strategies. Clin Lipidol. 2010 Jun;5(6):793-809. doi: 10.2217/clp.10.73. PMID: 22505953; PMCID: PMC3324780.