Abetalipoproteinemia: Difference between revisions

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*In 1960, Salt noticed the absence of [[serum]] beta-[[lipoprotein]] in the patient on [[electrophoresis]].<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 the patient on [[electrophoresis]].<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>
*The biochemical defect was determined to be a complete absence of [[apolipoprotein B]]-containing [[lipoproteins]]: [[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>
*The biochemical defect was determined to be a complete absence of [[apolipoprotein B]]-containing [[lipoproteins]]: [[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, [[apolipoprotein B]] content of the [[hepatocytes]], [[APOB]] gene and [[mRNA]] were found to be normal in patients with abetalipoproteinemia, suggesting a defective post-translational processing and secretion of apolipoprotein B as the cause of abetalipoproteinemia.<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, [[apolipoprotein B]] content of the [[hepatocytes]], [[APOB]] gene and [[mRNA]] were found to be normal in patients with abetalipoproteinemia, suggesting a defective [[post-translational]] processing and secretion of [[apolipoprotein B]] as the cause of abetalipoproteinemia.<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, [[Microsomal triglyceride transfer protein deficiency|microsomal triglyceride transfer protein]] (MTP) a deficiency due to the mutation reported as the primary cause of abetalipoproteinemia.<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, [[Microsomal triglyceride transfer protein deficiency|microsomal triglyceride transfer protein]] (MTP) a deficiency due to the mutation reported as the primary cause of abetalipoproteinemia.<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]] 4q 22-24 that encodes the large sub-unit of [[MTP]] was cloned and sequenced, and various human [[MTP]] mutations in abetalipoproteinemia 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]] 4q 22-24 that encodes the large sub-unit of [[MTP]] was cloned and sequenced, and various human [[MTP]] mutations in abetalipoproteinemia 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>
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== Natural History, Complications, and Prognosis ==
== 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.<ref name="urlOrphanet: Abetalipoproteinemia">{{cite web |url=http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=252&Disease_Disease_Search_diseaseGroup=Abetalipoproteinemia&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Abetalipoproteinemia&title=Abetalipoproteinemia&search=Disease_Search_Simple |title=Orphanet: Abetalipoproteinemia |format= |work= |accessdate=}}</ref>
*If left untreated, patients can develop atypical [[retinitis pigmentosa]], severe [[ataxia]], [[dysarthria]], and absent reflexes, leading to significant neurological functional impairment and reduced lifespan.<ref name="urlOrphanet: Abetalipoproteinemia">{{cite web |url=http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=252&Disease_Disease_Search_diseaseGroup=Abetalipoproteinemia&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Abetalipoproteinemia&title=Abetalipoproteinemia&search=Disease_Search_Simple |title=Orphanet: Abetalipoproteinemia |format= |work= |accessdate=}}</ref>
*Early identification and treatment with [[vitamin E]] can delay or prevent progression of the disease.<ref name="pmid11767031">{{cite journal| author=Chowers I, Banin E, Merin S, Cooper M, Granot E| title=Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. | journal=Eye (Lond) | year= 2001 | volume= 15 | issue= Pt 4 | pages= 525-30 | pmid=11767031 | doi=10.1038/eye.2001.167 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11767031  }} </ref> <ref name="pmid2981135">{{cite journal| author=Hegele RA, Angel A| title=Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy. | journal=Can Med Assoc J | year= 1985 | volume= 132 | issue= 1 | pages= 41-4 | pmid=2981135 | doi= | pmc=1346503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2981135  }} </ref>
*Early identification and treatment with [[vitamin E]] can delay and prevent progression of the disease.<ref name="pmid11767031">{{cite journal| author=Chowers I, Banin E, Merin S, Cooper M, Granot E| title=Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. | journal=Eye (Lond) | year= 2001 | volume= 15 | issue= Pt 4 | pages= 525-30 | pmid=11767031 | doi=10.1038/eye.2001.167 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11767031  }} </ref> <ref name="pmid2981135">{{cite journal| author=Hegele RA, Angel A| title=Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy. | journal=Can Med Assoc J | year= 1985 | volume= 132 | issue= 1 | pages= 41-4 | pmid=2981135 | doi= | pmc=1346503 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2981135  }} </ref>
*The [[prognosis]] is poor with a significantly reduced life expectancy.<ref name="urlOrphanet: Abetalipoproteinemia2">{{cite web |url=http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=252&Disease_Disease_Search_diseaseGroup=Abetalipoproteinemia&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Abetalipoproteinemia&title=Abetalipoproteinemia&search=Disease_Search_Simple |title=Orphanet: Abetalipoproteinemia |format= |work= |accessdate=}}</ref>
*The [[prognosis]] is poor with a significantly reduced life expectancy.<ref name="urlOrphanet: Abetalipoproteinemia2">{{cite web |url=http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=252&Disease_Disease_Search_diseaseGroup=Abetalipoproteinemia&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Abetalipoproteinemia&title=Abetalipoproteinemia&search=Disease_Search_Simple |title=Orphanet: Abetalipoproteinemia |format= |work= |accessdate=}}</ref>


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===History and Symptoms===
===History and Symptoms===
*Patients present in [[infancy]] with symptoms of [[Chronic diarrhea resident survival guide|chronic diarrhea]], [[steatorrhea]], [[failure to thrive]].
*Patients present in [[infancy]] with symptoms of [[Chronic diarrhea resident survival guide|chronic diarrhea]], [[steatorrhea]], [[failure to thrive]].
*The most serious symptoms are neurological due to [[demyelination]], which begins in the first or second decade of life and include:  
*The neurological symptoms due to [[demyelination]], which begins in the first or second decade of life and include:  
**Progressive truncal [[ataxia]] : Presents as instability   
**Progressive truncal [[ataxia]] : Presents as instability   
**Peripheral [[neuropathy]] causing [[numbness]], [[tingling]], weakness and [[parasthesias]].<ref name="pmid14237436">{{cite journal| author=SOBREVILLA LA, GOODMAN ML, KANE CA| title=DEMYELINATING CENTRAL NERVOUS SYSTEM DISEASE, MACULAR ATROPHY AND ACANTHOCYTOSIS (BASSEN-KORNZWEIG SYNDROME). | journal=Am J Med | year= 1964 | volume= 37 | issue=  | pages= 821-8 | pmid=14237436 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14237436  }} </ref>  
**Peripheral [[neuropathy]] causing [[numbness]], [[tingling]], weakness and [[parasthesias]].<ref name="pmid14237436">{{cite journal| author=SOBREVILLA LA, GOODMAN ML, KANE CA| title=DEMYELINATING CENTRAL NERVOUS SYSTEM DISEASE, MACULAR ATROPHY AND ACANTHOCYTOSIS (BASSEN-KORNZWEIG SYNDROME). | journal=Am J Med | year= 1964 | volume= 37 | issue=  | pages= 821-8 | pmid=14237436 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14237436  }} </ref>  
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Laboratory findings consistent with the diagnosis of abetalipoproteinemia include :
Laboratory findings consistent with the diagnosis of abetalipoproteinemia include :


*[[Lipid profile]] after a 12 hour fast will demonstrate low [[LDL]]C less than 0.1 mmol/L and [[triglyceride]] level of <0.2 mmol/L.<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>
*[[Lipid profile]] after a 12 hour fast will demonstrate a low [[LDL]]C less than 0.1 mmol/L and [[triglyceride]] level of <0.2 mmol/L.<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>
*Very low or undetectable [[vitamin E]] levels.
*Very low or undetectable [[vitamin E]] levels.
*Elevated [[liver function test]]s due to [[hepatic steatosis]].  
*Elevated [[liver function test]]s due to [[hepatic steatosis]].  
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*[[Peripheral blood smear]] demonstrates 50 to 90% of [[acanthocytes]], with increased [[erythrocyte fragility]].
*[[Peripheral blood smear]] demonstrates 50 to 90% of [[acanthocytes]], with increased [[erythrocyte fragility]].
*Absent [[beta-lipoprotein]] is demonstrated on 2D [[electrophoresis]].(apo B (<0.1 g/L)<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>
*Absent [[beta-lipoprotein]] is demonstrated on 2D [[electrophoresis]].(apo B (<0.1 g/L)<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>
*Gold standard test for diagnosing abetalipoproteinemia is [[molecular gene sequencing]] for MTTP gene.
*Gold standard test for diagnosing abetalipoproteinemia is molecular [[gene sequencing]] for MTTP gene.


===Approach to Low LDL C Algorithm===
===Approach to Low LDL C Algorithm===
The following algorithm helps to diagnose patients with low LDL C:
The following algorithm helps to diagnose patients with low [[LDL]] C:
{{Family tree/start}}
{{Family tree/start}}
{{Family tree | | | | | | A01 | | | |A01= Low [[LDL]] C <5th percentile}}
{{Family tree | | | | | | A01 | | | |A01= Low [[LDL]] C <5th percentile}}
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{{Family tree | | | | | | |!| | | | | }}
{{Family tree | | | | | | |!| | | | | }}
{{Family tree | | |,|-|-|-|^|-|-|.|}}
{{Family tree | | |,|-|-|-|^|-|-|.|}}
{{Family tree | |F01| | | | | | F02| |F01= Normal [[Triglycerides]]| F02=Low [[Triglycerides]]}}
{{Family tree | | F01 | | | | | F02| |F01= Normal [[Triglycerides]]| F02=Low [[Triglycerides]]}}
{{Family tree | |!| | | | | | | |!| | | | | | }}
{{Family tree | | |!| | | | | | |!| | | | | | }}
{{Family tree | G01 | | | | | | G02 | | | | | | |G01=Chlyomicron retention disease <br><SMALL>(Confirm with gene sequencing)</SMALL>| G02=Screen the [[lipid profile of the patient's parents}}
{{Family tree | | G01 | | | | | G02 | | |G01= [[Chlyomicron retention disease]] <br> <SMALL>(Confirm with [[gene sequencing]])</SMALL>| G02=Screen the [[lipid profile]] of the patient's parents}}
{{Family tree | | | | | | | | | |!| | | | }}
{{Family tree | | | | | | | | | |!| | | | }}
{{Family tree | | | | | | | |,|-|^|-|-|.| }}
{{Family tree | | | | | | | |,|-|^|-|-|.| }}
{{Family tree | | | | | | | H01| | |H02|H01=Normal Parental [[Lipid Profile]]|H02=If Parental [[Lipid profile]] <50% of Normal on:<br>*[[LDL]]<br>*[[Total Cholesterol]]<br>*[[Triglycerides]]}}
{{Family tree | | | | | | | H01| | |H02|H01=Normal Parental [[Lipid Profile]]|H02=If Parental [[Lipid profile]] <50% of Normal on:<br>*[[LDL]]<br>*[[Total Cholesterol]]<br>*[[Triglycerides]] }}
{{Family tree | | | | | | | |!| | | | |!| }}
{{Family tree | | | | | | | |!| | | | |!| }}
{{Family tree | | | | | | |I01| | |I02|I01=Abetalipoproteinemia<br><SMALL>(Confirm with [[gene sequencing]])</SMALL>|I02=[[Familial homozygous hypobetalipoproteinemia]]<br><SMALL>(Confirm with [[gene sequencing]])</SMALL>}}
{{Family tree | | | | | | |I01| | |I02|I01=Abetalipoproteinemia<br><SMALL>(Confirm with [[gene sequencing]])</SMALL>|I02=[[Familial homozygous hypobetalipoproteinemia]]<br><SMALL>(Confirm with [[gene sequencing]])</SMALL>}}
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== Differential Diagnosis ==
== Differential Diagnosis ==
Initial approach to a patient with steatorrhea requires a general approach to rule out the congenital causes of diarrhea and then consider the rarer causes like abetalipoproteinemia.<ref name="pmid22605972">{{cite journal| author=Terrin G, Tomaiuolo R, Passariello A, Elce A, Amato F, Di Costanzo M et al.| title=Congenital diarrheal disorders: an updated diagnostic approach. | journal=Int J Mol Sci | year= 2012 | volume= 13 | issue= 4 | pages= 4168-85 | pmid=22605972 | doi=10.3390/ijms13044168 | pmc=3344208 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22605972  }} </ref> <ref name="pmid26747865">{{cite journal| author=Overeem AW, Posovszky C, Rings EH, Giepmans BN, van IJzendoorn SC| title=The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders. | journal=Dis Model Mech | year= 2016 | volume= 9 | issue= 1 | pages= 1-12 | pmid=26747865 | doi=10.1242/dmm.022269 | pmc=4728335 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26747865  }} </ref>
Initial approach to a patient with [[steatorrhea]] requires a general approach to rule out the congenital causes of [[diarrhea]] and then consider the rarer causes like abetalipoproteinemia.<ref name="pmid22605972">{{cite journal| author=Terrin G, Tomaiuolo R, Passariello A, Elce A, Amato F, Di Costanzo M et al.| title=Congenital diarrheal disorders: an updated diagnostic approach. | journal=Int J Mol Sci | year= 2012 | volume= 13 | issue= 4 | pages= 4168-85 | pmid=22605972 | doi=10.3390/ijms13044168 | pmc=3344208 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22605972  }} </ref> <ref name="pmid26747865">{{cite journal| author=Overeem AW, Posovszky C, Rings EH, Giepmans BN, van IJzendoorn SC| title=The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders. | journal=Dis Model Mech | year= 2016 | volume= 9 | issue= 1 | pages= 1-12 | pmid=26747865 | doi=10.1242/dmm.022269 | pmc=4728335 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26747865  }} </ref>


The table below summarizes the diseases that have similar presentation as abetalipoproteinemia<ref name="pmid22027213">{{cite journal| author=Jung HH, Danek A, Walker RH| title=Neuroacanthocytosis syndromes. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue=  | pages= 68 | pmid=22027213 | doi=10.1186/1750-1172-6-68 | pmc=3212896 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22027213  }} </ref>:
The table below summarizes the diseases that have similar presentation as abetalipoproteinemia<ref name="pmid22027213">{{cite journal| author=Jung HH, Danek A, Walker RH| title=Neuroacanthocytosis syndromes. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue=  | pages= 68 | pmid=22027213 | doi=10.1186/1750-1172-6-68 | pmc=3212896 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22027213  }} </ref>:
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! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Abetalipoproteinemia (Autosomal Recessive)]]'''
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Abetalipoproteinemia]] <br> [[Autosomal recessive]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
* Mutation in MTP gene.
* [[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.  
*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.  
*Characteristic labs include absent [[LDL]] C, [[apolipoprotein B]] and [[acanthocytosis]].  
*Parents of the affected patient have normal lipid and Apo-B levels.
*Parents of the affected patient have normal [[lipid]] and [[apolipoprotein B]] levels.
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Hypobetalipoproteinemia (Autosomal Co-dominant)]]'''
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Hypobetalipoproteinemia]]<br>[[Autosomal co-dominant]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Mutation in APOB gene.  
* 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.
*It difficult to differentiate between homozygous hypobetalipoproteinemia and abetalipoproteinemia as they have similar clinical features and laboratory findings, only differentiating feature is that, parents of affected patient have decreased [[lipid]] levels and [[apolipoprotein B]] in [[homozygous]] [[hypobetalipoproteinemia]].
*Heterozygous patients have one-fourth to one-third of normal LDL C, Apo B and hepatic steatosis.
*[[Heterozygous]] patients have one-fourth to one-third of normal [[LDL]] C, [[apolipoprotein B]] and [[hepatic steatosis]].
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Fredrich Ataxia (Autosomal recessive)]]'''
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Fredrich Ataxia]]<br>[[Autosomal recessive]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
*Mutation in the FXN gene leads to triplet repeat expansion.  
*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.  
*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.<ref name="pmid26688047">{{cite journal| author=Rezende TJ, Silva CB, Yassuda CL, Campos BM, D'Abreu A, Cendes F et al.| title=Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia. | journal=Mov Disord | year= 2016 | volume= 31 | issue= 1 | pages= 70-8 | pmid=26688047 | doi=10.1002/mds.26436 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26688047  }} </ref>
*[[MRI]] show widespread white and gray matter damage in the infratentorial and supratentorial areas.<ref name="pmid26688047">{{cite journal| author=Rezende TJ, Silva CB, Yassuda CL, Campos BM, D'Abreu A, Cendes F et al.| title=Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia. | journal=Mov Disord | year= 2016 | volume= 31 | issue= 1 | pages= 70-8 | pmid=26688047 | doi=10.1002/mds.26436 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26688047  }} </ref>
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vitamin E deficiency secondary to fat malabsorption]]'''
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vitamin E deficiency]] <br> secondary to [[fat malabsorption]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |  
| style="padding: 5px 5px; background: #F5F5F5;" |  
*Seen in patients diagnosed with cystic fibrosis, pancreatic insufficiency, crohn's disease or liver disease.
*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.
* 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.
* Characteristic labs include low [[vitamin E]] and [[acanthocytosis]] with increased [[erythrocyte]] fragility.
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[McLeod Syndrome (X-Linked Recessive]]'''
| style="padding: 5px 5px; background: #DCDCDC;" |'''[[McLeod Syndrome]]<br>[[X-linked recessive]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Mutation in XK gene.  
*Mutation in XK gene.  
*Usually presents with chorea, cognitive impairment, psychiatric symptoms and diminished deep tendon reflexes.  
*Usually presents with [[chorea]], [[cognitive impairment]], psychiatric symptoms and diminished deep tendon reflexes.  
*Characteristic laboratory finding includes acanthocytosis.<ref name="pmid22027213">{{cite journal| author=Jung HH, Danek A, Walker RH| title=Neuroacanthocytosis syndromes. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue=  | pages= 68 | pmid=22027213 | doi=10.1186/1750-1172-6-68 | pmc=3212896 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22027213  }} </ref>
*Characteristic laboratory finding includes [[acanthocytosis]].<ref name="pmid22027213">{{cite journal| author=Jung HH, Danek A, Walker RH| title=Neuroacanthocytosis syndromes. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue=  | pages= 68 | pmid=22027213 | doi=10.1186/1750-1172-6-68 | pmc=3212896 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22027213  }} </ref>
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[HARP syndrome (Autosomal Recessive)]]'''
| style="padding: 5px 5px; background: #DCDCDC;" | '''[[HARP syndrome]]<br>[[Autosomal recessive]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Mutation in Pantothenate kinase 2.
*Mutation in Pantothenate kinase 2.
*HARP: hypoprebetalipoproteinema, acanthocytosis, retinitis pigmentosa, pallidal degeneration.
*HARP: hypoprebetalipoproteinema, [[acanthocytosis]], [[retinitis pigmentosa]], pallidal degeneration.
*Presents with orofacial dyskinesia, dystonia, dysarthria, rigidity and choreoathetosis and retinal 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.<ref name="pmid12058097">{{cite journal| author=Ching KH, Westaway SK, Gitschier J, Higgins JJ, Hayflick SJ| title=HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. | journal=Neurology | year= 2002 | volume= 58 | issue= 11 | pages= 1673-4 | pmid=12058097 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12058097  }} </ref>
*Characteristic labs include low prebetalipoprotein, [[acanthocytosis]] and on [[MRI]] pallidal degeneration is noticed.<ref name="pmid12058097">{{cite journal| author=Ching KH, Westaway SK, Gitschier J, Higgins JJ, Hayflick SJ| title=HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. | journal=Neurology | year= 2002 | volume= 58 | issue= 11 | pages= 1673-4 | pmid=12058097 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12058097  }} </ref>
|-
|-
|}
|}
Line 160: Line 160:


=== Medical Therapy ===
=== Medical Therapy ===
The main stay of therapy for abetalipoproteinemia is fat soluble vitamin supplementation, monitoring the progression of growth, and early identification and treatment of complications.  
The main stay of medical therapy for abetalipoproteinemia is [[fat soluble vitamin]] supplementation, monitoring the progression of growth, and early identification and treatment of complications.  
*High dose oral [[vitamin E]] supplementation therapy, 150-300mg/kg/day helps in preventing and reversal of [[neurological]] symptoms.  
*High dose oral [[vitamin E]] supplementation therapy, 150-300mg/kg/day helps in preventing and reversal of [[neurological]] symptoms.  
**Dosing and efficacy can be assessed by checking the Vitamin E levels in the [[adipose tissue]] [[Needle aspiration biopsy|needle aspiration biopsy.]]<ref name="pmid6959555">{{cite journal| author=Muller DP, Lloyd JK| title=Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia. | journal=Ann N Y Acad Sci | year= 1982 | volume= 393 | issue=  | pages= 133-44 | pmid=6959555 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6959555  }} </ref> <ref name="pmid19158321">{{cite journal| author=Iqbal J, Hussain MM| title=Intestinal lipid absorption. | journal=Am J Physiol Endocrinol Metab | year= 2009 | volume= 296 | issue= 6 | pages= E1183-94 | pmid=19158321 | doi=10.1152/ajpendo.90899.2008 | pmc=2692399 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19158321  }} </ref>
**Dosing and efficacy can be assessed by checking the Vitamin E levels in the [[adipose tissue]] [[Needle aspiration biopsy|needle aspiration biopsy.]]<ref name="pmid6959555">{{cite journal| author=Muller DP, Lloyd JK| title=Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia. | journal=Ann N Y Acad Sci | year= 1982 | volume= 393 | issue=  | pages= 133-44 | pmid=6959555 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6959555  }} </ref> <ref name="pmid19158321">{{cite journal| author=Iqbal J, Hussain MM| title=Intestinal lipid absorption. | journal=Am J Physiol Endocrinol Metab | year= 2009 | volume= 296 | issue= 6 | pages= E1183-94 | pmid=19158321 | doi=10.1152/ajpendo.90899.2008 | pmc=2692399 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19158321  }} </ref>
* Oral supplementation of Vitamin A 100–400 IU/kg/day; Vitamin D 800–1200 IU/day; Vitamin K 5–35 mg/week.<ref name="pmid848999">{{cite journal| author=Muller DP, Lloyd JK, Bird AC| title=Long-term management of abetalipoproteinaemia. Possible role for vitamin E. | journal=Arch Dis Child | year= 1977 | volume= 52 | issue= 3 | pages= 209-14 | pmid=848999 | doi= | pmc=1546285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=848999  }} </ref>
* Oral supplementation of [[Vitamin A]] 100–400 IU/kg/day; [[Vitamin D]] 800–1200 IU/day; [[Vitamin K]] 5–35 mg/week.<ref name="pmid848999">{{cite journal| author=Muller DP, Lloyd JK, Bird AC| title=Long-term management of abetalipoproteinaemia. Possible role for vitamin E. | journal=Arch Dis Child | year= 1977 | volume= 52 | issue= 3 | pages= 209-14 | pmid=848999 | doi= | pmc=1546285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=848999  }} </ref>
*Diet modification to control gastrointestinal symptoms. Low fat diet consisting of less than 30 % of  daily requirement of calories with reduced long-chain fatty acids and oral essential fatty acids is recommended.
*[[Parental]] supplementation of fat soluble vitamins is not preferred due to the risk of [[hepatic steatosis]].<ref name="pmid9745481">{{cite journal| author=Cavicchi M, Crenn P, Beau P, Degott C, Boutron MC, Messing B| title=Severe liver complications associated with long-term parenteral nutrition are dependent on lipid parenteral input. | journal=Transplant Proc | year= 1998 | volume= 30 | issue= 6 | pages= 2547 | pmid=9745481 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9745481  }} </ref>
*Parental supplementation of fat soluble vitamins is avoided due to the risk of hepatic steatosis.<ref name="pmid9745481">{{cite journal| author=Cavicchi M, Crenn P, Beau P, Degott C, Boutron MC, Messing B| title=Severe liver complications associated with long-term parenteral nutrition are dependent on lipid parenteral input. | journal=Transplant Proc | year= 1998 | volume= 30 | issue= 6 | pages= 2547 | pmid=9745481 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9745481  }} </ref>
*Diet modification is advised for control gastrointestinal symptoms, [[low fat diet]] consisting of less than 30 % of  daily requirement with reduced [[long-chain fatty acids]] and oral [[essential fatty acid]]s is recommended.


=== Surgery ===
=== Surgery ===
Line 175: Line 175:
=== Secondary Prevention ===
=== Secondary Prevention ===
Secondary prevention strategies following abetalipoproteinemia include:
Secondary prevention strategies following abetalipoproteinemia include:
*Monitoring growth in children and to delay neurological complications.<ref name="pmid848999">{{cite journal| author=Muller DP, Lloyd JK, Bird AC| title=Long-term management of abetalipoproteinaemia. Possible role for vitamin E. | journal=Arch Dis Child | year= 1977 | volume= 52 | issue= 3 | pages= 209-14 | pmid=848999 | doi= | pmc=1546285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=848999  }} </ref>
*Monitoring [[growth]] in children and to delay neurological complications.<ref name="pmid848999">{{cite journal| author=Muller DP, Lloyd JK, Bird AC| title=Long-term management of abetalipoproteinaemia. Possible role for vitamin E. | journal=Arch Dis Child | year= 1977 | volume= 52 | issue= 3 | pages= 209-14 | pmid=848999 | doi= | pmc=1546285 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=848999  }} </ref>
*Assessment for ataxia, dysarthria, visual changes every 6 to 12 months.
*Assessment 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 regularly.<ref name="pmid18611256">{{cite journal| author=Zamel R, Khan R, Pollex RL, Hegele RA| title=Abetalipoproteinemia: two case reports and literature review. | journal=Orphanet J Rare Dis | year= 2008 | volume= 3 | issue=  | pages= 19 | pmid=18611256 | doi=10.1186/1750-1172-3-19 | pmc=2467409 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18611256  }} </ref>
*As [[vitamin]] levels do not return to normal even after years of treatment, it's recommended to assess for features of deficiency regularly.<ref name="pmid18611256">{{cite journal| author=Zamel R, Khan R, Pollex RL, Hegele RA| title=Abetalipoproteinemia: two case reports and literature review. | journal=Orphanet J Rare Dis | year= 2008 | volume= 3 | issue=  | pages= 19 | pmid=18611256 | doi=10.1186/1750-1172-3-19 | pmc=2467409 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18611256  }} </ref>


==References==
==References==

Latest revision as of 16:00, 29 March 2017

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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 is a very rare autosomal recessive disease due to mutation in MTP gene on chromosome 4q23. MTP encodes for microsomal triglyceride transport protein, which catalyses the intracellular transport of triglyceride, cholesterol esters and phospholipids from the cytosol onto the apolipoprotein B present in the endoplasmic reticulum. Mutation in MTP gene results in the failure of formation and secretion of chylomicrons, LDL and VLDL which accumulate in the intestine and liver. Characteristic features of abetalipoproteinemia include steatorrhea, retinitis pigmentosa, ataxia, acanthocytosis, low or undetectable LDL and apolipoprotein B. Patients present in infancy with steatorrhea and failure to thrive. Asymptomatic patients in infancy are usually diagnosed in adulthood with symptoms of neuropathy. Fat malabsorption results in the deficiency of fat soluble vitamins and essential fatty acids, features of vitamin E deficiency are seen early in the disease, as the vitamin E levels are dependent on the total lipid levels in the body. Early diagnosis and initiation of vitamin E supplementation is helpful to stop the progression of disease and in reversal of neurological damage.

Historical Perspective

Pathophysiology

Pathogenesis

Genetics

Microscopic Findings

On microscopic examination:

Screening

Epidemiology and Demographics

  • Worldwide, the prevalence of abetalipoproteinemia is reported to be less than 1 in 1,000,000.[15]
  • 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.[14]
  • Early identification and treatment with vitamin E can delay and prevent progression of the disease.[16] [17]
  • The prognosis is poor with a significantly reduced life expectancy.[18]

Diagnosis

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

History and Symptoms

Physical Examination

Physical examination of patients with abetalipoproteinemia is remarkable for:

Laboratory Findings

Laboratory findings consistent with the diagnosis of abetalipoproteinemia include :

Approach to Low LDL C Algorithm

The following algorithm helps to diagnose patients with low LDL C:

 
 
 
 
 
Low LDL C <5th percentile
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rule out secondary causes of low LDL
Anemia
Criticial illness
Chronic inflammation
Chronic liver disease
Hyperthyroidism
Infection
Malabsorption
Malignancy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Consider primary monogenic causes based on lipid profile
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal Triglycerides
 
 
 
 
Low Triglycerides
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chlyomicron retention disease
(Confirm with gene sequencing)
 
 
 
 
Screen the lipid profile of the patient's parents
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal Parental Lipid Profile
 
 
If Parental Lipid profile <50% of Normal on:
*LDL
*Total Cholesterol
*Triglycerides
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abetalipoproteinemia
(Confirm with gene sequencing)
 
 
Familial homozygous hypobetalipoproteinemia
(Confirm with gene sequencing)

Differential Diagnosis

Initial approach to a patient with steatorrhea requires a general approach to rule out the congenital causes of diarrhea and then consider the rarer causes like abetalipoproteinemia.[22] [23]

The table below summarizes the diseases that have similar presentation as abetalipoproteinemia[24]:

Disease Findings
Abetalipoproteinemia
Autosomal recessive
Hypobetalipoproteinemia
Autosomal co-dominant
Fredrich Ataxia
Autosomal recessive
Vitamin E deficiency
secondary to fat malabsorption
McLeod Syndrome
X-linked recessive
HARP syndrome
Autosomal recessive

Treatment

Medical Therapy

The main stay of medical therapy for abetalipoproteinemia is fat soluble vitamin supplementation, monitoring the progression of growth, and early identification and treatment of complications.

Surgery

Surgical intervention is not recommended for the management of abetalipoproteinemia.

Primary Prevention

There are no primary preventive measures available for abetalipoproteinemia.

Secondary Prevention

Secondary prevention strategies following abetalipoproteinemia include:

  • Monitoring growth in children and to delay neurological complications.[29]
  • Assessment for ataxia, dysarthria, visual changes every 6 to 12 months.
  • As vitamin levels do not return to normal even after years of treatment, it's recommended to assess for features of deficiency regularly.[31]

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. 14.0 14.1 "Orphanet: Abetalipoproteinemia".
  15. 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.
  16. 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.
  17. 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.
  18. "Orphanet: Abetalipoproteinemia".
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