Abetalipoproteinemia (Bassen Kornzweig Syndrome)

Abetalipoproteinemia - very high mag[1]

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 originates from this process: metabolic.

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].

Entire body system
neurologic
  • Ataxia 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. [source] They can include poor muscle coordination, difficulty with balance and movement (ataxia), and progressive degeneration of the retina (the light-sensitive layer in the posterior eye) that can progress to near-blindness (due to deficiency of vitamin A, [source]
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gastrointestinal
  • Diarrhea 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. [source] Diarrhea, failure to thrive, acanthocytosis and central nervous system complications are most important features. [source] Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome. [source]
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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.

Laboratory

Serum

Treatment

Prognosis

Complications

  • Malabsorption Syndrome Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome[source]
  • Retinitis Pigmentosa pigmentosa Hypocholesterolemia/low blood cholesterol Abetalipoproteinemia affects the absorption of dietary fats, cholesterol, and certain vitamins. [source] abdomen Intellectual disability/developmental delay Developmental coordination disorder, evident by age ten Muscle weakness Slurred speech Scoliosis (curvature of the spine) Progressive decreased vision Balance and coordination problems Acanthocytosis Retinitis [source]
  • Scoliosis thrive/Failure to grow in infancy Steatorrhea/Fatty, pale stools Frothy stools Foul smelling stools Protruding abdomen Intellectual disability/developmental delay Developmental coordination disorder, evident by age ten Muscle weakness Slurred speech Scoliosis [source]
  • Vitamin A Deficiency However, many of the observed effects are due to vitamin E deficiency in particular. [source] Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts. [source] This leads to a multiple vitamin deficiency, affecting the fat-soluble vitamin A, vitamin D, vitamin E, and vitamin K. [source]
  • Vitamin E Deficiency However, many of the observed effects are due to vitamin E deficiency in particular. [source] Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts. [source]
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Etiology

Epidemiology

Sex distribution
Age distribution

Pathophysiology

Prevention

Summary

Patient Information

Self-assessment

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.

  • Anesthesia for genetic, metabolic, and dysmorphic syndromes of childhood - VC Baum, JE O'Flaherty - 2006 - books.google.com
  • 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
  • Abetalipoproteinemia: two case reports and literature review - R Zamel, R Khan, RL Pollex, RA Hegele - Orphanet J Rare , 2008 - biomedcentral.com
  • 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
  • Abetalipoproteinemia (Bassen-Kornzweig syndrome) - E Kott, G Delpre, U Kadish, M Dziatelovsky - Acta , 1977 - Springer
  • 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
  • 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
  • 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
  • Abetalipoproteinemia in an Indian family - MV Padma, S Jain, MC Maheshwari - Indian journal of pediatrics, 1996 - Springer
  • 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
  • Abetalipoproteinemia and metastatic spinal cord glioblastoma - RP Newman, EJ Schaefer, CB Thomas - Archives of , 1984 - Am Med Assoc
  • 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
  • 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
  • Abetalipoproteinemia presenting as severe vitamin K deficiency - FM Caballero, GR Buchanan - Pediatrics, 1980 - Am Acad Pediatrics
  • A possible cause of decreased vision in cryptococcal meningitis - C KUPFER, E McCRANE - Investigative Ophthalmology & Visual Science, 1974 - ARVO
  • Abetalipoproteinemia: Metabolic, endocrine, and electron-microscopic investigations - MA Sperling, F Hengstenberg, E Yunis, FM Kenny - Pediatrics, 1971 - Am Acad Pediatrics
  • 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
  • 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
  • Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer

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