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*In 1960, Salt noticed the absence of serum beta-[[lipoprotein]] in a patient with the syndrome.<ref name="pmid13745738">{{cite journal| author=SALT HB, WOLFF OH, LLOYD JK, FOSBROOKE AS, CAMERON AH, HUBBLE DV| title=On having no beta-lipoprotein. A syndrome comprising a-beta-lipoproteinaemia, acanthocytosis, and steatorrhoea. | journal=Lancet | year= 1960 | volume= 2 | issue= 7146 | pages= 325-9 | pmid=13745738 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13745738  }} </ref>
*In 1960, Salt noticed the absence of serum beta-[[lipoprotein]] in a patient with the syndrome.<ref name="pmid13745738">{{cite journal| author=SALT HB, WOLFF OH, LLOYD JK, FOSBROOKE AS, CAMERON AH, HUBBLE DV| title=On having no beta-lipoprotein. A syndrome comprising a-beta-lipoproteinaemia, acanthocytosis, and steatorrhoea. | journal=Lancet | year= 1960 | volume= 2 | issue= 7146 | pages= 325-9 | pmid=13745738 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13745738  }} </ref>
*Eventually, the fundamental biochemical defect was determined to be a complete absence of [[plasma]] [[apolipoprotein]] (apo) B-containing lipoproteins, namely [[Chylomicron|chylomicrons]], very-low density lipoprotein ([[VLDL]]), and low-density lipoprotein ([[LDL]]).<ref name="pmid5245476">{{cite journal| author=Sturman RM| title=The Bassen-Kornzweig syndrome: 18 years in evolution. | journal=J Mt Sinai Hosp N Y | year= 1968 | volume= 35 | issue= 5 | pages= 489-517 | pmid=5245476 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5245476  }} </ref>
*Eventually, the fundamental biochemical defect was determined to be a complete absence of [[plasma]] [[apolipoprotein]] (apo) B-containing lipoproteins, namely [[Chylomicron|chylomicrons]], very-low density lipoprotein ([[VLDL]]), and low-density lipoprotein ([[LDL]]).<ref name="pmid5245476">{{cite journal| author=Sturman RM| title=The Bassen-Kornzweig syndrome: 18 years in evolution. | journal=J Mt Sinai Hosp N Y | year= 1968 | volume= 35 | issue= 5 | pages= 489-517 | pmid=5245476 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5245476  }} </ref>
* In 1986, the APOB gene, its [[mRNA]] and the apo B content of the [[hepatocytes]] were found to be normal in ABL patients, suggesting that defective post-translational processing and secretion of apo B was the cause of ABL.<ref name="pmid3782476">{{cite journal| author=Lackner KJ, Monge JC, Gregg RE, Hoeg JM, Triche TJ, Law SW et al.| title=Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. | journal=J Clin Invest | year= 1986 | volume= 78 | issue= 6 | pages= 1707-12 | pmid=3782476 | doi=10.1172/JCI112766 | pmc=423946 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3782476  }} </ref>
* In 1986, the APOB gene, its [[mRNA]], and the apo B content of the [[hepatocytes]] were found to be normal in ABL patients, suggesting that defective post-translational processing and secretion of apo B was the cause of ABL.<ref name="pmid3782476">{{cite journal| author=Lackner KJ, Monge JC, Gregg RE, Hoeg JM, Triche TJ, Law SW et al.| title=Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. | journal=J Clin Invest | year= 1986 | volume= 78 | issue= 6 | pages= 1707-12 | pmid=3782476 | doi=10.1172/JCI112766 | pmc=423946 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3782476  }} </ref>
*In 1992, a [[Microsomal triglyceride transfer protein deficiency|deficiency of microsomal triglyceride transfer protein]] (MTP) activity was suggested to be the proximal cause of ABL.<ref name="pmid1439810">{{cite journal| author=Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M et al.| title=Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. | journal=Science | year= 1992 | volume= 258 | issue= 5084 | pages= 999-1001 | pmid=1439810 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1439810  }} </ref>  
*In 1992, a [[Microsomal triglyceride transfer protein deficiency|deficiency of microsomal triglyceride transfer protein]] (MTP) activity was suggested to be the proximal cause of ABL.<ref name="pmid1439810">{{cite journal| author=Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M et al.| title=Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. | journal=Science | year= 1992 | volume= 258 | issue= 5084 | pages= 999-1001 | pmid=1439810 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1439810  }} </ref>  
*In 1993, the region on chromosome 4q22-24 that encodes the large subunit of MTP was cloned and sequenced, and human MTP mutations in ABL patients were reported.<ref name="pmid8111381">{{cite journal| author=Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT et al.| title=Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. | journal=Hum Mol Genet | year= 1993 | volume= 2 | issue= 12 | pages= 2109-16 | pmid=8111381 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8111381  }} </ref>
*In 1993, the region on chromosome 4q22-24 that encodes the large subunit of MTP was cloned and sequenced, and human MTP mutations in ABL patients were reported.<ref name="pmid8111381">{{cite journal| author=Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT et al.| title=Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. | journal=Hum Mol Genet | year= 1993 | volume= 2 | issue= 12 | pages= 2109-16 | pmid=8111381 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8111381  }} </ref>

Revision as of 19:17, 18 November 2016

Lipid Disorders Main Page

Overview

Causes

Classification

Abetalipoproteinemia
Hypobetalipoproteinemia
Familial hypoalphalipoproteinemia
LCAT Deficiency
Chylomicron retention disease
Tangier disease
Familial combined hypolipidemia

Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]

Synonyms and keywords: Acanthocytosis, Bassen-Kornzweig syndrome, apolipoprotein B deficiency, microsomal triglyceride transfer protein deficiency, MTP deficiency

Overview

Abetalipoproteinemia (APOB) is a disease with autosomal recessive inheritance. Abetalipoproteinemia (ABL; OMIM200100) and hypobetalipoproteinemia (HHBL; OMIM107730) together are reffered to as familial hypolipoproteinemia. This is a set of diseases characterized by low levels of low density lipoprotein (LDL). Characteristic presentation involves steatorrhea, atypical retinitis pigmentosa, and ataxia.

Historical Perspective

  • The first clinical association of peripheral blood acanthocytosis with atypical retinitis pigmentosa and ataxia was reported by Bassen and Kornzweig in 1950.[1]
  • In 1958, Jampel and Falls observed low serum cholesterol values in affected individuals.[2]
  • In 1960, Salt noticed the absence of serum beta-lipoprotein in a patient with the syndrome.[3]
  • Eventually, the fundamental biochemical defect was determined to be a complete absence of plasma apolipoprotein (apo) B-containing lipoproteins, namely chylomicrons, very-low density lipoprotein (VLDL), and low-density lipoprotein (LDL).[4]
  • In 1986, the APOB gene, its mRNA, and the apo B content of the hepatocytes were found to be normal in ABL patients, suggesting that defective post-translational processing and secretion of apo B was the cause of ABL.[5]
  • In 1992, a deficiency of microsomal triglyceride transfer protein (MTP) activity was suggested to be the proximal cause of ABL.[6]
  • In 1993, the region on chromosome 4q22-24 that encodes the large subunit of MTP was cloned and sequenced, and human MTP mutations in ABL patients were reported.[7]

Pathophysiology

Pathogenesis

  • MTTP catalyzes the transfer of triglycerides from the cytosol to ApoB in the endoplasmic reticulum which is necessary for the formation and eventual secretion of LDL, VLDL and chylomicrons[8].
  • The defect in the MTP causes accumalation of lipid in the intestine leading to Steatorrhea and malabsorption of fat soluble vitamins.
  • Accumalation of lipid in the liver causes hepatic steatosis.
  • The result of this excessive accumulation causes very low LDL C and VLDL.
  • Vitamin E deficiency features are more prominent because the absorption and transport of vitamin E is parallel to the total body lipid levels due to its hydrophobic nature.
    • Spinocerebellar and posterior columns are affected as only minimal amount of vitamin E was transported in HDL C resulting in neurological symptoms[9].

Genetics

  • Autosomal Recessive Inheritance.[10].[11]
  • Mutation of MTP (aka MTTP) gene which codes for the Microsomal Trigyceride transfer Protein, MTP.[6] [12]
  • MTTP gene mutation occurs on chromosome 4q 22-24[7], leads to the failure of formation and secretion of apolipoprotein B( Apo B) containing lipoproteins which include chylomicrons, LDL and VLDL from the intestine and liver.[13]
  • Patients with heterozygous expression have normal lipoprotein levels indicating that both the alleles of the gene coding for MTTP must be defective.

Microscopic Findings

  • Intestinal biopsy : Distended enterocytes strongly positive to oil red O indicates presence of intracellular lipid.[8]
  • Liver Biopsy: Hepatic Steatosis

Screening

  • Screening of parents of affected individuals show normal Apo B levels and LDL C levels consistent with autosomal recessive inheritance.

Epidemiology and Demographics

The incidence of ABL is reported less than 1 in 1,000,000.[14]. Males and females are affected equally.

Natural History, Complications, and Prognosis

  • If left untreated, patients can develop atypical retinitis pigmentosa, severe ataxia, dysarthria, and absent reflexes, leading to significant neurological functional impairment and reduced lifespan.
  • Early identification and treatment with vitamin E can delay or prevent progression of the disease.[15] [16]

Differential Diagnosis

  • Differentiate from congenital causes of diarrhea.[17] [18]
  • Hypobetalipoproteinemia: Homozygous patients have similar presentation and laboratory results.
  • Severe Vitamin E deficiency: Neurological Symptoms improve significantly with supplementation of Vitamin E.
  • Friedrich Ataxia.
  • X-Linked McLeod Disease: Presence of acanthocytes and ataxia. Additionally movement disorders and cognitive impairment are present.[19]

The table below summarizes the diseases that have similar presentation as Abetalipoproteinemia:

Disease Findings
Abetalipoproteinemia (Autosomal Recessive)
  • Mutation in MTP gene.
  • Presents in with Steatorrhea, progressive ataxia, dysarthria, loss of proprioceptive and vibration sense, diminished deep tendon reflexes, impaired visual acuity due to retinal degeneration.
  • Characteristic labs include absent LDL C, Apo B and acanthocytosis.
  • Parents of the affected patient have normal lipid and Apo-B levels.
Hypobetalipoproteinemia (Autosomal Co-dominant)
  • Mutation in APOB gene.
  • It difficult to differentiate between homozygous hypobetalipoproteinemia and ABL as they have similar clinical features and laboratory findings, only differentiating feature is that, parents of affected patient have decreased lipid levels and Apo B in homozygous hypobetalipoproteinemia.
  • Heterozygous patients have one-fourth to one-third of normal LDL C, Apo B and hepatic steatosis.
Fredrich Ataxia (Autosomal recessive)
  • Mutation in the FXN gene leads to triplet repeat expansion.
  • Clinical features include progressive ataxia and dysarthria, loss of proprioception and vibration sense, motor weakness, diminished deep tendon reflexes, impaired visual aquity due to optic atrophy.
  • MRI show widespread white and gray matter damage in the infratentorial and supratentorial areas.[20]
Vitamin E deficiency secondary to fat malabsorption
  • Seen in patients diagnosed with cystic fibrosis, pancreatic insufficiency, crohn's disease or liver disease.
  • Presents in with steatorrhea, progressive ataxia, loss of proprioceptive and vibration sense, diminished deep tendon reflexes, impaired visual acuity due to retinal degeneration.
  • Characteristic labs include low vitamin E and acanthocytosis with increased erythrocyte fragility.
McLeod Syndrome (X-Linked Recessive
  • Mutation in XK gene.
  • Usually presents with chorea, cognitive impairment, psychiatric symptoms and diminished deep tendon reflexes.
  • Characteristic laboratory finding includes acanthocytosis.[19]
HARP syndrome (Autosomal Recessive)
  • Mutation in Pantothenate kinase 2.
  • HARP: hypoprebetalipoproteinema, acanthocytosis, retinitis pigmentosa, pallidal degeneration.
  • Presents with orofacial dyskinesia, dystonia, dysarthria, rigidity and choreoathetosis and retinal degeneration.
  • Characteristic labs include lowprebetalipoprotein, acanthocytosis and on MRI pallidal degeneration is noticed.[21]

Diagnosis

Clinical diagnosis is made based on the symptoms, lipid profile and blood smear findings.

History and Symptoms

  • Patients present in infancy with symptoms of chronic diarrhea, steatorrhea, failure to thrive.
  • The most serious symptoms are neurological due to demyelination[22], which begins in the first or second decade of life and include progressive ataxia and peripheral neuropathy.
  • Less common symptoms due to long term fat soluble vitamin deficiency are:
    • Easy bruising
    • Osteomalacia
    • Loss of night vision is the first symptom of retinal degeneration which progresses to blindness.

Physical Examination

Specific physical exam findings include as follows:

  • Reduced Visual Acuity and degenerative changes in the retina are seen.
    • Fundoscopic examination reveals atypical dark pigmentation irregularly distributed on the retina, which left untreated will progress to expanding scotomas leading to blindness. [23]
  • Hepatomegaly
  • Neurological: The symptoms are secondary to demyleination.[22]
    • Truncal Ataxia due to the effect on spinocerebellar tracts.
    • Sensory Motor neuropathy presenting with weakness and muscular atrophy.
    • Loss of proprioception, vibration and temperature can be affected when the disease affects the posterior column.
    • Deep Tendon reflexes are diminished.

Laboratory Findings

Laboratory findings consistent with the diagnosis of abetalipoproteinemia include :

  • Lipid Profile: Low triglyceride and LDL C.(LDL-C (<0.1 mmol/L), TG (<0.2 mmol/L).[4]
  • Absent Beta-lipoprotien on electrophoresis.(apo B (<0.1 g/L)[5]
  • Gold Standard test : Molecular testing by sequencing the MTTP gene.
  • Peripheral smear shows 50 to 90% of acanthocytes, with increased erythrocyte fragility.
  • Very low or undetectable vitamin E levels.
  • Elevated LFT's due to hepatic steatosis.[24]

Treatment

Medical Therapy

  • High dose oral vitamin E supplementation therapy, 150-300mg/kg/day helps in preventing or reversal of the neurological symptoms.
  • Oral supplementation of Vitamin A 100–400 IU/kg/day -Vitamin D 800–1200 IU/day -Vitamin K 5–35 mg/week.[27]
  • Diet modification to control gastrointestinal symptoms.
    • Low fat (<30 % of total calories), with reduced long-chain fatty acids and oral essential fatty acids.
  • Parenteral supplementation is avoided due to the risk of hepatic steatosis.[28]

Surgery

Surgical intervention is not recommended for the management of ABL.

Primary Prevention

There are no primary preventive measures available for ABL.

Secondary Prevention

  • Goal is to monitor growth in children and to delay neurological complications.
  • Assesment for ataxia, dysarthria, visual changes every 6 to 12 months.
  • As vitamin levels don't return to normal even after years of treatment, it's recommended to assess for deficiencies.[29]


References

  1. ↑ BASSEN FA, KORNZWEIG AL (1950). "Malformation of the erythrocytes in a case of atypical retinitis pigmentosa". Blood. 5 (4): 381–87. PMID 15411425.
  2. ↑ JAMPEL RS, FALLS HF (1958). "Atypical retinitis pigmentosa, acanthrocytosis, and heredodegenerative neuromuscular disease". AMA Arch Ophthalmol. 59 (6): 818–20. PMID 13532088.
  3. ↑ SALT HB, WOLFF OH, LLOYD JK, FOSBROOKE AS, CAMERON AH, HUBBLE DV (1960). "On having no beta-lipoprotein. A syndrome comprising a-beta-lipoproteinaemia, acanthocytosis, and steatorrhoea". Lancet. 2 (7146): 325–9. PMID 13745738.
  4. ↑ 4.0 4.1 Sturman RM (1968). "The Bassen-Kornzweig syndrome: 18 years in evolution". J Mt Sinai Hosp N Y. 35 (5): 489–517. PMID 5245476.
  5. ↑ 5.0 5.1 Lackner KJ, Monge JC, Gregg RE, Hoeg JM, Triche TJ, Law SW; et al. (1986). "Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia". J Clin Invest. 78 (6): 1707–12. doi:10.1172/JCI112766. PMC 423946. PMID 3782476.
  6. ↑ 6.0 6.1 Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M; et al. (1992). "Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia". Science. 258 (5084): 999–1001. PMID 1439810.
  7. ↑ 7.0 7.1 Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT; et al. (1993). "Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein". Hum Mol Genet. 2 (12): 2109–16. PMID 8111381.
  8. ↑ 8.0 8.1 Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M, Wetterau JR (2000). "The role of the microsomal triglygeride transfer protein in abetalipoproteinemia". Annu Rev Nutr. 20: 663–97. doi:10.1146/annurev.nutr.20.1.663. PMID 10940349.
  9. ↑ Bjornson LK, Kayden HJ, Miller E, Moshell AN (1976). "The transport of alpha-tocopherol and beta-carotene in human blood". J Lipid Res. 17 (4): 343–52. PMID 181502.
  10. ↑ Lee J, Hegele RA (2014). "Abetalipoproteinemia and homozygous hypobetalipoproteinemia: a framework for diagnosis and management". J Inherit Metab Dis. 37 (3): 333–9. doi:10.1007/s10545-013-9665-4. PMID 24288038.
  11. ↑ Burnett JR, Bell DA, Hooper AJ, Hegele RA (2015). "Clinical utility gene card for: Abetalipoproteinaemia--Update 2014". Eur J Hum Genet. 23 (6). doi:10.1038/ejhg.2014.224. PMC 4795071. PMID 25335492.
  12. ↑ Walsh MT, Iqbal J, Josekutty J, Soh J, Di Leo E, Özaydin E; et al. (2015). "Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N-Terminal β-Barrel in Microsomal Triglyceride Transfer Protein Function". Circ Cardiovasc Genet. 8 (5): 677–87. doi:10.1161/CIRCGENETICS.115.001106. PMC 4618089. PMID 26224785.
  13. ↑ Hussain MM, Rava P, Walsh M, Rana M, Iqbal J (2012). "Multiple functions of microsomal triglyceride transfer protein". Nutr Metab (Lond). 9: 14. doi:10.1186/1743-7075-9-14. PMC 3337244. PMID 22353470.
  14. ↑ Burnett JR, Bell DA, Hooper AJ, Hegele RA (2012). "Clinical utility gene card for: Abetalipoproteinaemia". Eur J Hum Genet. 20 (8). doi:10.1038/ejhg.2012.30. PMC 3400737. PMID 22378282.
  15. ↑ Chowers I, Banin E, Merin S, Cooper M, Granot E (2001). "Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients". Eye (Lond). 15 (Pt 4): 525–30. doi:10.1038/eye.2001.167. PMID 11767031.
  16. ↑ Hegele RA, Angel A (1985). "Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy". Can Med Assoc J. 132 (1): 41–4. PMC 1346503. PMID 2981135.
  17. ↑ Terrin G, Tomaiuolo R, Passariello A, Elce A, Amato F, Di Costanzo M; et al. (2012). "Congenital diarrheal disorders: an updated diagnostic approach". Int J Mol Sci. 13 (4): 4168–85. doi:10.3390/ijms13044168. PMC 3344208. PMID 22605972.
  18. ↑ Overeem AW, Posovszky C, Rings EH, Giepmans BN, van IJzendoorn SC (2016). "The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders". Dis Model Mech. 9 (1): 1–12. doi:10.1242/dmm.022269. PMC 4728335. PMID 26747865.
  19. ↑ 19.0 19.1 Jung HH, Danek A, Walker RH (2011). "Neuroacanthocytosis syndromes". Orphanet J Rare Dis. 6: 68. doi:10.1186/1750-1172-6-68. PMC 3212896. PMID 22027213.
  20. ↑ Rezende TJ, Silva CB, Yassuda CL, Campos BM, D'Abreu A, Cendes F; et al. (2016). "Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia". Mov Disord. 31 (1): 70–8. doi:10.1002/mds.26436. PMID 26688047.
  21. ↑ Ching KH, Westaway SK, Gitschier J, Higgins JJ, Hayflick SJ (2002). "HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration". Neurology. 58 (11): 1673–4. PMID 12058097.
  22. ↑ 22.0 22.1 SOBREVILLA LA, GOODMAN ML, KANE CA (1964). "DEMYELINATING CENTRAL NERVOUS SYSTEM DISEASE, MACULAR ATROPHY AND ACANTHOCYTOSIS (BASSEN-KORNZWEIG SYNDROME)". Am J Med. 37: 821–8. PMID 14237436.
  23. ↑ Runge P, Muller DP, McAllister J, Calver D, Lloyd JK, Taylor D (1986). "Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia". Br J Ophthalmol. 70 (3): 166–73. PMC 1040960. PMID 3954973.
  24. ↑ Di Filippo M, Moulin P, Roy P, Samson-Bouma ME, Collardeau-Frachon S, Chebel-Dumont S; et al. (2014). "Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia". J Hepatol. 61 (4): 891–902. doi:10.1016/j.jhep.2014.05.023. PMID 24842304.
  25. ↑ Muller DP, Lloyd JK (1982). "Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia". Ann N Y Acad Sci. 393: 133–44. PMID 6959555.
  26. ↑ Iqbal J, Hussain MM (2009). "Intestinal lipid absorption". Am J Physiol Endocrinol Metab. 296 (6): E1183–94. doi:10.1152/ajpendo.90899.2008. PMC 2692399. PMID 19158321.
  27. ↑ Muller DP, Lloyd JK, Bird AC (1977). "Long-term management of abetalipoproteinaemia. Possible role for vitamin E." Arch Dis Child. 52 (3): 209–14. PMC 1546285. PMID 848999.
  28. ↑ Cavicchi M, Crenn P, Beau P, Degott C, Boutron MC, Messing B (1998). "Severe liver complications associated with long-term parenteral nutrition are dependent on lipid parenteral input". Transplant Proc. 30 (6): 2547. PMID 9745481.
  29. ↑ Zamel R, Khan R, Pollex RL, Hegele RA (2008). "Abetalipoproteinemia: two case reports and literature review". Orphanet J Rare Dis. 3: 19. doi:10.1186/1750-1172-3-19. PMC 2467409. PMID 18611256.


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