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Familial hypobetalipoproteinemia 2(FHBL2)

MedGen UID:
341895
Concept ID:
C1857970
Disease or Syndrome
Synonym: HYPOLIPIDEMIA, FAMILIAL, COMBINED
 
Gene (location): ANGPTL3 (1p31.3)
 
Monarch Initiative: MONDO:0011505
OMIM®: 605019

Definition

Hypobetalipoproteinemia (HBL) is defined as permanently low levels, below the 5th percentile of sex- and age-matched individuals in the population, of apolipoprotein B (apoB), total cholesterol, and low-density lipoprotein (LDL) cholesterol; the lipid profile in FHBL2 includes low HDL cholesterol as well. HBL can result from environmental factors such as a strict vegetarian diet, or can be secondary to certain diseases such as intestinal fat malabsorption, chronic pancreatitis, severe liver disease, malnutrition, or hyperthyroidism. Heritable primary causes of HBL include chylomicron retention disease (CMRD; 246700), abetalipoproteinemia (200100), and familial hypobetalipoproteinemia (FHBL) (summary by Martin-Campos et al., 2012). For a discussion of genetic heterogeneity of familial hypobetalipoproteinemia, see FHBL1 (615558). [from OMIM]

Additional description

From MedlinePlus Genetics
Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. This condition is characterized by low levels of a fat-like substance called cholesterol in the blood. The severity of signs and symptoms experienced by people with FHBL vary widely. The most mildly affected individuals have few problems with absorbing fats from the diet and no related signs and symptoms. Many individuals with FHBL develop an abnormal buildup of fats in the liver called hepatic steatosis or fatty liver. In more severely affected individuals, fatty liver may progress to chronic liver disease (cirrhosis). Individuals with severe FHBL have greater difficulty absorbing fats as well as fat-soluble vitamins such as vitamin E and vitamin A. This difficulty in fat absorption leads to excess fat in the feces (steatorrhea). In childhood, these digestive problems can result in an inability to grow or gain weight at the expected rate (failure to thrive).  https://medlineplus.gov/genetics/condition/familial-hypobetalipoproteinemia

Clinical features

From HPO
Hypotriglyceridemia
MedGen UID:
488913
Concept ID:
C0542037
Disease or Syndrome
An decrease in the level of triglycerides in the blood.
Decreased LDL cholesterol concentration
MedGen UID:
776554
Concept ID:
C0853085
Finding
An decreased concentration of low-density lipoprotein cholesterol in the blood.

Professional guidelines

PubMed

Long MT, Noureddin M, Lim JK
Gastroenterology 2022 Sep;163(3):764-774.e1. Epub 2022 Jul 14 doi: 10.1053/j.gastro.2022.06.023. PMID: 35842345Free PMC Article
Takahashi M, Okazaki H, Ohashi K, Ogura M, Ishibashi S, Okazaki S, Hirayama S, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Oct 1;28(10):1009-1019. Epub 2021 May 16 doi: 10.5551/jat.RV17056. PMID: 33994405Free PMC Article
Bredefeld C, Peretti N, Hussain MM; Medical Advisory Panel
Gastroenterology 2021 May;160(6):1912-1916. Epub 2020 Dec 1 doi: 10.1053/j.gastro.2020.11.040. PMID: 33275938

Recent clinical studies

Etiology

Long MT, Noureddin M, Lim JK
Gastroenterology 2022 Sep;163(3):764-774.e1. Epub 2022 Jul 14 doi: 10.1053/j.gastro.2022.06.023. PMID: 35842345Free PMC Article
Welty FK
Curr Opin Lipidol 2020 Apr;31(2):49-55. doi: 10.1097/MOL.0000000000000663. PMID: 32039990
Noto D, Arca M, Tarugi P, Cefalù AB, Barbagallo CM, Averna MR
Acta Diabetol 2017 Feb;54(2):111-122. Epub 2016 Nov 2 doi: 10.1007/s00592-016-0931-4. PMID: 27804036
Jung HH, Danek A, Walker RH
Orphanet J Rare Dis 2011 Oct 25;6:68. doi: 10.1186/1750-1172-6-68. PMID: 22027213Free PMC Article
Moutzouri E, Elisaf M, Liberopoulos EN
Curr Vasc Pharmacol 2011 Mar;9(2):200-12. doi: 10.2174/157016111794519354. PMID: 20626336

Diagnosis

Long MT, Noureddin M, Lim JK
Gastroenterology 2022 Sep;163(3):764-774.e1. Epub 2022 Jul 14 doi: 10.1053/j.gastro.2022.06.023. PMID: 35842345Free PMC Article
Welty FK
Curr Opin Lipidol 2020 Apr;31(2):49-55. doi: 10.1097/MOL.0000000000000663. PMID: 32039990
Noto D, Arca M, Tarugi P, Cefalù AB, Barbagallo CM, Averna MR
Acta Diabetol 2017 Feb;54(2):111-122. Epub 2016 Nov 2 doi: 10.1007/s00592-016-0931-4. PMID: 27804036
Jung HH, Danek A, Walker RH
Orphanet J Rare Dis 2011 Oct 25;6:68. doi: 10.1186/1750-1172-6-68. PMID: 22027213Free PMC Article
Moutzouri E, Elisaf M, Liberopoulos EN
Curr Vasc Pharmacol 2011 Mar;9(2):200-12. doi: 10.2174/157016111794519354. PMID: 20626336

Therapy

Rimbert A, Yeung MW, Dalila N, Thio CHL, Yu H, Loaiza N, Oldoni F, van der Graaf A, Wang S, Said MA, Blauw LL, Girardeau A, Bray L, Caillaud A, Bloks VW, Marrec M, Moulin P, Rensen PCN, van de Sluis B, Snieder H, Di Filippo M, van der Harst P, Tybjaerg-Hansen A, Zimmerman P, Cariou B, Kuivenhoven JA
Arterioscler Thromb Vasc Biol 2022 Oct;42(10):1262-1271. Epub 2022 Sep 1 doi: 10.1161/ATVBAHA.122.317514. PMID: 36047410
Legland Ép Dejean AM, Plantamura J, Arnoux I, Paleiron N, Loosveld M, Buono Ép Foucher B
Br J Haematol 2022 Apr;197(2):131. Epub 2022 Feb 7 doi: 10.1111/bjh.18020. PMID: 35128635
Welty FK
Curr Opin Lipidol 2020 Apr;31(2):49-55. doi: 10.1097/MOL.0000000000000663. PMID: 32039990
Hooper AJ, Heeks L, Robertson K, Champain D, Hua J, Song S, Parhofer KG, Barrett PH, van Bockxmeer FM, Burnett JR
J Clin Endocrinol Metab 2015 Nov;100(11):E1484-90. Epub 2015 Aug 31 doi: 10.1210/jc.2015-2731. PMID: 26323024
Cullen P, Funke H, Schulte H, Assmann G
J Atheroscler Thromb 1997;4(2):51-8. doi: 10.5551/jat1994.4.51. PMID: 9638514

Prognosis

Rimbert A, Yeung MW, Dalila N, Thio CHL, Yu H, Loaiza N, Oldoni F, van der Graaf A, Wang S, Said MA, Blauw LL, Girardeau A, Bray L, Caillaud A, Bloks VW, Marrec M, Moulin P, Rensen PCN, van de Sluis B, Snieder H, Di Filippo M, van der Harst P, Tybjaerg-Hansen A, Zimmerman P, Cariou B, Kuivenhoven JA
Arterioscler Thromb Vasc Biol 2022 Oct;42(10):1262-1271. Epub 2022 Sep 1 doi: 10.1161/ATVBAHA.122.317514. PMID: 36047410
Long MT, Noureddin M, Lim JK
Gastroenterology 2022 Sep;163(3):764-774.e1. Epub 2022 Jul 14 doi: 10.1053/j.gastro.2022.06.023. PMID: 35842345Free PMC Article
Takahashi M, Okazaki H, Ohashi K, Ogura M, Ishibashi S, Okazaki S, Hirayama S, Hori M, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Oct 1;28(10):1009-1019. Epub 2021 May 16 doi: 10.5551/jat.RV17056. PMID: 33994405Free PMC Article
Jung HH, Danek A, Walker RH
Orphanet J Rare Dis 2011 Oct 25;6:68. doi: 10.1186/1750-1172-6-68. PMID: 22027213Free PMC Article
Palau F, Espinós C
Orphanet J Rare Dis 2006 Nov 17;1:47. doi: 10.1186/1750-1172-1-47. PMID: 17112370Free PMC Article

Clinical prediction guides

Rimbert A, Yeung MW, Dalila N, Thio CHL, Yu H, Loaiza N, Oldoni F, van der Graaf A, Wang S, Said MA, Blauw LL, Girardeau A, Bray L, Caillaud A, Bloks VW, Marrec M, Moulin P, Rensen PCN, van de Sluis B, Snieder H, Di Filippo M, van der Harst P, Tybjaerg-Hansen A, Zimmerman P, Cariou B, Kuivenhoven JA
Arterioscler Thromb Vasc Biol 2022 Oct;42(10):1262-1271. Epub 2022 Sep 1 doi: 10.1161/ATVBAHA.122.317514. PMID: 36047410
Long MT, Noureddin M, Lim JK
Gastroenterology 2022 Sep;163(3):764-774.e1. Epub 2022 Jul 14 doi: 10.1053/j.gastro.2022.06.023. PMID: 35842345Free PMC Article
Calandra S, Tarugi P, Bertolini S
Curr Opin Lipidol 2011 Apr;22(2):93-9. doi: 10.1097/MOL.0b013e3283426ebc. PMID: 21157333
Tarugi P, Averna M, Di Leo E, Cefalù AB, Noto D, Magnolo L, Cattin L, Bertolini S, Calandra S
Atherosclerosis 2007 Dec;195(2):e19-27. Epub 2007 Jun 14 doi: 10.1016/j.atherosclerosis.2007.05.003. PMID: 17570373
Schonfeld G
Annu Rev Nutr 1995;15:23-34. doi: 10.1146/annurev.nu.15.070195.000323. PMID: 8527219

Recent systematic reviews

Noto D, Arca M, Tarugi P, Cefalù AB, Barbagallo CM, Averna MR
Acta Diabetol 2017 Feb;54(2):111-122. Epub 2016 Nov 2 doi: 10.1007/s00592-016-0931-4. PMID: 27804036

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