Abetalipoproteinemia

Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability of the body to absorb lipoproteins from the gastroenterological system due to mutations of proteins responsible for their transport across enterocytes. Diarrhea, failure to thrive, acanthocytosis and central nervous system complications are most important features. The diagnosis requires a thorough diagnostic workup, including laboratory and genetic studies.

The disease is related to the following processes:  metabolic and has an incidence of about  1 / 100.000.

Overview

Etiology

Epidemiology

Sex distribution
Age distribution

Pathophysiology

Prognosis

Presentation

The clinical presentation of abetalipoproteinemia (ABL) stems from an insufficient physiological transport of plasma B-containing lipoproteins - chylomicrons, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), due to mutations of the microsomal triglyceride transfer protein (MTP), responsible for their transfer through enterocytes [1] [2]. Malabsorption of fat and fat-soluble vitamins, principal pathological events, lead to a very early onset of failure to thrive, reduced growth and severe fatty diarrhea (steatorrhea) [1] [3]. Gradually, diarrhea can subside as patients learn to avoid foods that have shown to induce diarrhea, but the deficiency of fat-soluble vitamins can cause numerous symptoms [1] [3]. Central nervous system damage and visual deficits, due to deficiencies of vitamins E and A, respectively, are most important long-term complications. Reduced deep-tendon reflexes, dysmetria, ataxia, diminished proprioception and vibratory sense, as well as progressive neuropathy, may develop in the first two decades of life [1] [4]. Conversely, pigmentary retinopathy leads to scotomas, loss of color and night vision, and even blindness [1] [4]. Additional complications that have been documented in the literature include coagulopathies (due to vitamin K deficiency), myopathy and demyelination that can cause a spastic gait, while reduced fertility is also reported [1] [2] [4].

Workup

Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome. For this reason, a detailed patient history regarding the onset and course of symptoms is detrimental. In addition, a complete physical examination can detect signs of malnourishment, defects in both lower and upper motor neurons, as well as hepatomegaly and visual deficits, strengthening its equally important role in workup [1]. Laboratory studies will reveal minimal or absent low-density lipoprotein (LDL) and triglycerides, whereas increased liver enzymes (alanine and aspartate aminotransferases, or ALT and AST) due to frequent hepatic steatosis are readily observed [2]. A complete blood count (CBC) with a subsequent peripheral blood smear demarcates the presence of acanthocytes, abnormally shaped cells that comprise up to 50% of visible erythrocytes [1] [2], and their presence is considered a cardinal feature of ABL. Moreover, a profoundly reduced erythrocyte sedimentation rate (ESR), anemia and elevated prothrombin time (PT) are other notable findings, suggesting that a full coagulation panel should be included in initial workup [1]. If clinical and laboratory findings provide sufficient evidence to pursue a diagnosis of ABL, genetic testing must be conducted, even without a positive family history, which is common due to the autosomal recessive pattern of inheritance and frequent absence of symptoms in both parents. Detection of mutations in the MTP protein located on chromosome 4q22-24 will confirm the diagnosis [1]. Hepatomegaly may be seen as a result of steatosis of liver. The biopsy of liver in the diseased patients may reveal steatosis along with the raise in the level of serum transaminase.

Treatment

Prevention

Patient Information

Search symptoms now!

References

  1. Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet Journal of Rare Diseases. 2008;3:19.
  2. Ferreira F, Patel V, Matts S. A successful spontaneous pregnancy in abetalipoproteinemia: Amsterdam or the art of vitamin replacement? BMJ Case Rep. 2014;2014:bcr2014206754.
  3. Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015;88(Pt A):59-62.
  4. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.

  • Abetalipoproteinemia [OMIM# 200100] - AJ Larner - 2011 - Springer
  • AAEM minimonograph# 34: polyneuropathy: classification by nerve conduction studies and electromyography - PD Donofrio, JW Albers - Muscle & nerve, 1990 - Wiley Online Library
  • APPROACH TO A FIVE YEAR OLD WHO PRESENTS WITH ONE MONTH HISTORY OF ATAXIA - M IYPE - NEUROPED 2011 PG TRAINING PROGRAM AND , 2011 - iapkerala.org
  • Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer
  • Abetalipoproteinemia (Bassen-Kornzweig syndrome) - E Kott, G Delpre, U Kadish, M Dziatelovsky - Acta , 1977 - Springer
  • A clinical and neurophysiological investigation of a Danish kindred with heterozygous familial hypobetalipoproteinemia - GE Andersen, W Trojaborg, HC Lou - Acta Paediatrica, 2008 - Wiley Online Library
  • Anesthesia for genetic, metabolic, and dysmorphic syndromes of childhood - VC Baum, JE O'Flaherty - 2006 - books.google.com
  • Abetalipoproteinemia in an Indian family - MV Padma, S Jain, MC Maheshwari - Indian journal of pediatrics, 1996 - Springer
  • A possible cause of decreased vision in cryptococcal meningitis - C KUPFER, E McCRANE - Investigative Ophthalmology & Visual Science, 1974 - ARVO
  • Acanthocytosis Without - EMR Critchley, DB Clark, A Wikler - Archives of Neurology, 1968 - Am Med Assoc
  • Abetalipoproteinemia - D Pautler, D Easley, JF Pohl - Journal of pediatric , 2008 - journals.lww.com
  • A paucity of colonic enteroendocrine and/or enterochromaffin cells characterizes a subset of patients with chronic unexplained diarrhea/malabsorption - S Ohsie, G Gerney, D Gui, D Kahana, MG Martín - Human pathology, 2009 - Elsevier
  • Abetalipoproteinemia: Metabolic, endocrine, and electron-microscopic investigations - MA Sperling, F Hengstenberg, E Yunis, FM Kenny - Pediatrics, 1971 - Am Acad Pediatrics
  • Abetalipoproteinemia: two case reports and literature review - R Zamel, R Khan, RL Pollex, RA Hegele - Orphanet J Rare , 2008 - biomedcentral.com
  • Clinical and genetic abnormalities in patients with Friedreich's ataxia - A Dürr, M Cossee, Y Agid, V Campuzano - England Journal of , 1996 - Mass Medical Soc
  • A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus - K Ohashi, S Ishibashi, M Yamamoto - , and vascular biology, 1998 - Am Heart Assoc
  • Abetalipoproteinemia presenting as severe vitamin K deficiency - FM Caballero, GR Buchanan - Pediatrics, 1980 - Am Acad Pediatrics
  • Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families - L Cavalier, K Ouahchi, HJ Kayden, S Di Donato - The American Journal of , 1998 - Elsevier
  • A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X–linked retinitis pigmentosa (RP3) - A Meindl, K Dry, K Herrmann, E Manson - Nature , 1996 - nature.com
  • With accumulation of an apoprotein B-like protein in intestinal cells. Immunoenzymatic and biochemical characterization of seven cases of Anderson's disease. - ME Bouma, I Beucler, LP Aggerbeck - Journal of Clinical , 1986 - ncbi.nlm.nih.gov
  • Abetalipoproteinemia and metastatic spinal cord glioblastoma - RP Newman, EJ Schaefer, CB Thomas - Archives of , 1984 - Am Med Assoc
Search symptoms now!