Hypobetalipoproteinemia: Difference between revisions
Jump to navigation
Jump to search
| Line 14: | Line 14: | ||
===Pathogenesis=== | ===Pathogenesis=== | ||
*Cholesterol and triglycerides are insolublei in the plasma, so they require a transport protien in the form of apolipoprotein B. These lipoproteins transport cholesterol and trigylcerides in spherical particles in which the cholesterol esters and triglyceride form the central core. | |||
*Apolipoprotein B is the major carrier for triglycerides and cholesterol from the intestine and liver to the periphery. | |||
*Apo B exits in two forms, Apo B48 and Apo B100. | |||
{{Family tree/start}} | |||
{{Family tree | | | | A01 | | | |A01= Apo B48 is produced in intestine and is critical in the formation and secretion of chylomicrons , Apo B100 is synthesized in liver and released into circulation as VLDL}} | |||
{{Family tree | | | | |!| | | | | }} | |||
{{Family tree | | | | B01 | | | |B01= MTP transfers triglycerides from cytsol onto nacent ApoB in endoplasmic reticulum which is required for assembly and secretion of VLDL and chylomicrons }} | |||
{{Family tree | | | | |!| | | | | }} | |||
{{Family tree | | | | C01 | | | |C01= In the periphery by the action of lipoprotein lipase in the endothelium of the capillaries and glycosylphosphatidylinositol-anchored high-density lipoprotein- binding protein 1 (GPIHBP1) triglycerides are hydrolysed to form free fatty acids and glycerol }} | |||
{{Family tree | | | | |!| | | | | }} | |||
{{Family tree | | | | D01 | | | |D01= This results in the formation of VLDL remnant( Intermediate density lipoprotein) and chylomicron remnants | |||
The lipases are inhibited by Angiopoietin-like protein 3 (ANGPTL3) thereby decreasing the triglyceride and LDL C.}} | |||
{{Family tree | | | | |!| | | | | }} | |||
{{Family tree | | | | E01 | | | |E01= IDL on further removal of triglycerides forms a cholesterol ester rich LDL C}} | |||
{{Family tree | | | | |!| | | | | }} | |||
{{Family tree | | | | F01 | | | |F01=LDL C is removed from the circulation by binding to LDL receptors in the liver. The receptor degradation is enhanced by Proprotein convertase subtilisin kexin 9 (PCSK9), any mutation in the loss of function in the enzyme causes low LDL C levels}} | |||
{{Family tree/end}} | |||
===Genetics=== | ===Genetics=== | ||
Revision as of 16:52, 15 November 2016
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: Familial hypobetalipoproteinemia, FHBL, normotriglyceridemic hypobetalipoproteinemia
Overview
It is a rare disease caused by mutation in the APOB gene or less commonly in the PCSK9 gene, characteristic findings include low plasma level of total cholesterol, low LDL C, and Apo B below the 5th percentile when compared to the normal population.
Historical Perspective
- In 1960, Salt reported absence of betalipoprotein in the plasma of a patient associated with very low cholesterol levels in the parents. Low cholesterol levels in the parents differentiates it from abetalipoproteinemia[1].
Pathophysiology
Pathogenesis
- Cholesterol and triglycerides are insolublei in the plasma, so they require a transport protien in the form of apolipoprotein B. These lipoproteins transport cholesterol and trigylcerides in spherical particles in which the cholesterol esters and triglyceride form the central core.
- Apolipoprotein B is the major carrier for triglycerides and cholesterol from the intestine and liver to the periphery.
- Apo B exits in two forms, Apo B48 and Apo B100.
| Apo B48 is produced in intestine and is critical in the formation and secretion of chylomicrons , Apo B100 is synthesized in liver and released into circulation as VLDL | |||||||||||||||||||
| MTP transfers triglycerides from cytsol onto nacent ApoB in endoplasmic reticulum which is required for assembly and secretion of VLDL and chylomicrons | |||||||||||||||||||
| In the periphery by the action of lipoprotein lipase in the endothelium of the capillaries and glycosylphosphatidylinositol-anchored high-density lipoprotein- binding protein 1 (GPIHBP1) triglycerides are hydrolysed to form free fatty acids and glycerol | |||||||||||||||||||
| This results in the formation of VLDL remnant( Intermediate density lipoprotein) and chylomicron remnants The lipases are inhibited by Angiopoietin-like protein 3 (ANGPTL3) thereby decreasing the triglyceride and LDL C. | |||||||||||||||||||
| IDL on further removal of triglycerides forms a cholesterol ester rich LDL C | |||||||||||||||||||
| LDL C is removed from the circulation by binding to LDL receptors in the liver. The receptor degradation is enhanced by Proprotein convertase subtilisin kexin 9 (PCSK9), any mutation in the loss of function in the enzyme causes low LDL C levels | |||||||||||||||||||
Genetics
- Mutation in the APOB gene on chromosome 2p24 which codes for apolipoprotein B.
- Mutation in the PCSK9 can also cause the disease but it is less common compared to the mutation in Apo B.
- Familial hypobetalipoproteinemia-2 is caused by mutation in the ANGPTL3 gene (604774) on chromosome 1p31.
Natural History, complications and Prognosis
Diagnosis
History and Physical
Laboratory Results
Treatment=
Medical Therapy
Surgical Therapy
Prevention
Hypobetalipoproteinemia is a rare autosomal dominant genetic disorder causing abnormally low levels of LDL cholesterol and apolipoprotein B.[2] It is thought to be caused by a mutation in apolipoprotein B.[3] The patient can have low LDL level and simultaneously have high levels of HDL cholesterol. Typically in hypobtalipoproteinemia, plasma cholesterol levels will be around 80-120 mg/dL, LDL cholesterol will be around 50-80 mg/dL, and longevity can be expected with good nutrition. Affected individuals can be either homozygous or heterozygous, the latter being most commonly asymptomatic.[3]
Normotriglyceridemic hypobetalipoproteinemia, formally called normotriglyceridemic abetalipoproteinemia, is a condition characterized by absence of LDLs and apoB100 and normal triglyceride-rich lipoproteins.[4][5]
References
- ↑ 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.
- ↑ Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C; et al. (2010). "Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia". N Engl J Med. 363 (23): 2220–7. doi:10.1056/NEJMoa1002926. PMC 3008575. PMID 20942659.
- ↑ 3.0 3.1 Schonfeld G, Lin X, Yue P (2005). "Familial hypobetalipoproteinemia: genetics and metabolism". Cell Mol Life Sci. 62 (12): 1372–8. doi:10.1007/s00018-005-4473-0. PMID 15818469.
- ↑ Harano Y, Kojima H, Nakano T, Harada M, Kashiwagi A, Nakajima Y; et al. (1989). "Homozygous hypobetalipoproteinemia with spared chylomicron formation". Metabolism. 38 (1): 1–7. PMID 2909827.
- ↑ Herbert PN, Hyams JS, Bernier DN, Berman MM, Saritelli AL, Lynch KM; et al. (1985). "Apolipoprotein B-100 deficiency. Intestinal steatosis despite apolipoprotein B-48 synthesis". J Clin Invest. 76 (2): 403–12. doi:10.1172/JCI111986. PMC 423826. PMID 4031057.
- ↑ Biemer JJ, McCammon RE (1975). "The genetic relationship of abetalipoproteinemia and hypobetalipoproteinemia: a report of the occurence of both diseases within the same family". J Lab Clin Med. 85 (4): 556–65. PMID 164511.