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Hyperlipoproteinemia, type I

MedGen UID:
7352
Concept ID:
C0023817
Disease or Syndrome
Synonyms: Familial chylomicronemia; Familial hyperlipo-proteinemia type 1; Familial Lipoprotein Lipase Deficiency; Hyperchylomicro-nemia familial; Hyperlipemia essential familial; Hyperlipemia idiopathic Burger-Grutz type; Hyperlipoproteinemia type 1; HYPERLIPOPROTEINEMIA, TYPE IA; Lipase D deficiency; Lipoprotein lipase deficiency; LPL deficiency
SNOMED CT: Familial lipoprotein lipase deficiency with type I phenotype (403827000); Familial type I hyperlipoproteinemia (403827000); Familial lipoprotein lipase deficiency (275598004); Familial hyperlipoproteinemia, type I (275598004); Fredrickson type 1 hyperlipoproteinemia (275598004); Hyperchylomicronemia (267435002); Primary hyperchylomicronemia (267435002); Familial hyperchylomicronemia (267435002); Burger-Grutz syndrome (267435002); Hepatosplenomegalic lipoidosis (275598004); Hyperlipoproteinemia, type I (275598004); Endogenous hypertriglyceridemia (275598004); Hypercholesterinemic xanthomatosis (275598004); Familial fat-induced hypertriglyceridemia (275598004)
 
Gene (location): LPL (8p21.3)
 
Monarch Initiative: MONDO:0009387
OMIM®: 238600
Orphanet: ORPHA309015

Disease characteristics

Excerpted from the GeneReview: Familial Lipoprotein Lipase Deficiency
Familial lipoprotein lipase (LPL) deficiency usually presents in childhood and is characterized by very severe hypertriglyceridemia with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. Clearance of chylomicrons from the plasma is impaired, causing triglycerides to accumulate in plasma and the plasma to have a milky (lactescent or lipemic) appearance. Symptoms usually resolve with restriction of total dietary fat to ≤20 g/day. [from GeneReviews]
Authors:
John R Burnett  |  Amanda J Hooper  |  Robert A Hegele   view full author information

Additional description

From MedlinePlus Genetics
Familial lipoprotein lipase deficiency is an inherited condition that disrupts the normal breakdown of fats in the body, resulting in an increase of certain kinds of fats.

People with familial lipoprotein lipase deficiency typically develop signs and symptoms before age 10, with one-quarter showing symptoms by age 1. The first symptom of this condition is usually abdominal pain, which can vary from mild to severe. The abdominal pain is often due to inflammation of the pancreas (pancreatitis). These episodes of pancreatitis begin as sudden (acute) attacks. If left untreated, pancreatitis can develop into a chronic condition that can damage the pancreas and, in rare cases, be life-threatening.

Affected individuals may also have an enlarged liver and spleen (hepatosplenomegaly). The higher the levels of fat in the body, the larger the liver and spleen become. As fat levels rise, certain white blood cells called macrophages take in excess fat in an attempt to rid fat from the bloodstream. After taking in fat, the macrophages travel to the liver and spleen, where the fatty cells accumulate.

Approximately half of individuals with familial lipoprotein lipase deficiency develop small yellow deposits of fat under the skin called eruptive xanthomas. These fat deposits most commonly appear on the trunk, buttocks, knees, and arms. Eruptive xanthomas are small (about 1 millimeter in diameter), but individual xanthomas can cluster together to form larger patches. They are generally not painful unless exposed to repeated friction or abrasion. Eruptive xanthomas begin to appear when fat intake increases and levels rise; the deposits disappear when fat intake slows and levels decrease.

The blood of people with familial lipoprotein lipase deficiency can have a milky appearance due to its high fat content. When fat levels get very high in people with this condition, fats can accumulate in blood vessels in the tissue that lines the back of the eye (the retina). The fat buildup gives this tissue a pale pink appearance when examined (lipemia retinalis). This fat accumulation does not affect vision and will disappear once fats from the diet are reduced and levels in the body decrease.

In people with familial lipoprotein lipase deficiency, increased fat levels can also cause neurological features, such as depression, memory loss, and mild intellectual decline (dementia). These problems are remedied when dietary fat levels normalize.  https://medlineplus.gov/genetics/condition/familial-lipoprotein-lipase-deficiency

Clinical features

From HPO
Episodic abdominal pain
MedGen UID:
814352
Concept ID:
C3808022
Finding
An intermittent form of abdominal pain.
Precocious atherosclerosis
MedGen UID:
867292
Concept ID:
C4021654
Pathologic Function
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Nausea
MedGen UID:
10196
Concept ID:
C0027497
Sign or Symptom
A sensation of unease in the stomach together with an urge to vomit.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Acute pancreatitis
MedGen UID:
7872
Concept ID:
C0001339
Disease or Syndrome
A acute form of pancreatitis.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Hyperlipidemia
MedGen UID:
5692
Concept ID:
C0020473
Disease or Syndrome
An elevated lipid concentration in the blood.
Lactescent serum
MedGen UID:
1377499
Concept ID:
C1096710
Finding
Serum sample with a grossly white (milk-like, i.e., lactescent) appearance. This feature is indicative of an extremely elevated serum triglyceride level.
Increased circulating chylomicron concentration
MedGen UID:
853340
Concept ID:
C1535978
Finding
Increased plasma concentrations of chylomicrons, the large lipid droplet (up to 100 mm in diameter) of reprocessed lipid synthesized in epithelial cells of the small intestine and containing triacylglycerols, cholesterol esters, and several apolipoproteins.
Eruptive xanthomas
MedGen UID:
66366
Concept ID:
C0221252
Disease or Syndrome
Eruptive xanthomas are yellow-orange-to-red-brown papules that are often surrounded by an erythematous halo. They appear in crops on the buttocks, extensor surfaces of the extremities, and flexural creases. Acutely, variable amounts of pruritus and pain occur.
Lipemia retinalis
MedGen UID:
137918
Concept ID:
C0339477
Disease or Syndrome
A creamy appearance of the retinal blood vessels that occurs when the concentration of lipids in the blood are extremely increased, with pale pink to milky white retinal vessels and altered pale reflexes from choroidal vasculature.

Term Hierarchy

Follow this link to review classifications for Hyperlipoproteinemia, type I in Orphanet.

Professional guidelines

PubMed

Gotoda T, Shirai K, Ohta T, Kobayashi J, Yokoyama S, Oikawa S, Bujo H, Ishibashi S, Arai H, Yamashita S, Harada-Shiba M, Eto M, Hayashi T, Sone H, Suzuki H, Yamada N; Research Committee for Primary Hyperlipidemia, Research on Measures against Intractable Diseases by the Ministry of Health, Labour and Welfare in Japan
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Recent clinical studies

Etiology

Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, Hegele RA, Arca M, Ballantyne CM, Soran H, Prohaska TA, Xia S, Ginsberg HN, Witztum JL, Tsimikas S; Balance Investigators
N Engl J Med 2024 May 16;390(19):1781-1792. Epub 2024 Apr 7 doi: 10.1056/NEJMoa2400201. PMID: 38587247
Malick WA, Do R, Rosenson RS
Pharmacol Ther 2023 Nov;251:108544. Epub 2023 Oct 15 doi: 10.1016/j.pharmthera.2023.108544. PMID: 37848164
Wierzbicki AS, Kim EJ, Esan O, Ramachandran R
J Clin Pathol 2022 Dec;75(12):798-806. Epub 2022 Jun 16 doi: 10.1136/jclinpath-2021-207719. PMID: 35710321
Goldberg RB, Chait A
Front Endocrinol (Lausanne) 2020;11:593931. Epub 2020 Oct 23 doi: 10.3389/fendo.2020.593931. PMID: 33193106Free PMC Article
Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E
N Engl J Med 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944. PMID: 31390500

Diagnosis

Wierzbicki AS, Kim EJ, Esan O, Ramachandran R
J Clin Pathol 2022 Dec;75(12):798-806. Epub 2022 Jun 16 doi: 10.1136/jclinpath-2021-207719. PMID: 35710321
Gouni-Berthold I, Alexander VJ, Yang Q, Hurh E, Steinhagen-Thiessen E, Moriarty PM, Hughes SG, Gaudet D, Hegele RA, O'Dea LSL, Stroes ESG, Tsimikas S, Witztum JL; COMPASS study group
Lancet Diabetes Endocrinol 2021 May;9(5):264-275. Epub 2021 Mar 30 doi: 10.1016/S2213-8587(21)00046-2. PMID: 33798466
Kuthiroly S, Yesodharan D, Radhakrishnan N, Ganapathy A, Mannan AU, Hoffmann MM, Nampoothiri S
Indian J Pediatr 2021 Feb;88(2):147-153. Epub 2020 May 30 doi: 10.1007/s12098-020-03305-z. PMID: 32472350
Falko JM
Endocr Pract 2018 Aug;24(8):756-763. doi: 10.4158/EP-2018-0157. PMID: 30183397
Chait A, Brunzell JD
Adv Intern Med 1992;37:249-73. PMID: 1557997

Therapy

Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, Hegele RA, Arca M, Ballantyne CM, Soran H, Prohaska TA, Xia S, Ginsberg HN, Witztum JL, Tsimikas S; Balance Investigators
N Engl J Med 2024 May 16;390(19):1781-1792. Epub 2024 Apr 7 doi: 10.1056/NEJMoa2400201. PMID: 38587247
Chait A
Curr Opin Endocrinol Diabetes Obes 2024 Apr 1;31(2):78-83. Epub 2023 Nov 23 doi: 10.1097/MED.0000000000000846. PMID: 37994661
Wierzbicki AS, Kim EJ, Esan O, Ramachandran R
J Clin Pathol 2022 Dec;75(12):798-806. Epub 2022 Jun 16 doi: 10.1136/jclinpath-2021-207719. PMID: 35710321
Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, Yang Q, Hughes SG, Geary RS, Arca M, Stroes ESG, Bergeron J, Soran H, Civeira F, Hemphill L, Tsimikas S, Blom DJ, O'Dea L, Bruckert E
N Engl J Med 2019 Aug 8;381(6):531-542. doi: 10.1056/NEJMoa1715944. PMID: 31390500
Ewang-Emukowhate M, Wierzbicki AS
J Cardiovasc Pharmacol Ther 2013 Sep;18(5):401-11. Epub 2013 Jun 27 doi: 10.1177/1074248413492906. PMID: 23811423

Prognosis

Okazaki H, Gotoda T, Ogura M, Ishibashi S, Inagaki K, Daida H, Hayashi T, Hori M, Masuda D, Matsuki K, Yokoyama S, Harada-Shiba M
J Atheroscler Thromb 2021 Sep 1;28(9):883-904. Epub 2021 May 13 doi: 10.5551/jat.RV17054. PMID: 33980761Free PMC Article
Gouni-Berthold I, Alexander VJ, Yang Q, Hurh E, Steinhagen-Thiessen E, Moriarty PM, Hughes SG, Gaudet D, Hegele RA, O'Dea LSL, Stroes ESG, Tsimikas S, Witztum JL; COMPASS study group
Lancet Diabetes Endocrinol 2021 May;9(5):264-275. Epub 2021 Mar 30 doi: 10.1016/S2213-8587(21)00046-2. PMID: 33798466
Dib I, Khalil A, Chouaib R, El-Makhour Y, Noureddine H
Mol Biol Rep 2021 Jan;48(1):875-886. Epub 2021 Jan 3 doi: 10.1007/s11033-020-06071-5. PMID: 33389539Free PMC Article
Gabcova-Balaziova D, Stanikova D, Vohnout B, Huckova M, Stanik J, Klimes I, Raslova K, Gasperikova D
Endocr Regul 2015 Jul;49(3):164-81. doi: 10.4149/endo_2015_03_164. PMID: 26238499
Chait A, Brunzell JD
Adv Intern Med 1992;37:249-73. PMID: 1557997

Clinical prediction guides

Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, Moriarty PM, Rubba P, Whitcomb DC, Banerjee P, Gewitz A, Gonzaga-Jauregui C, McGinniss J, Ponda MP, Pordy R, Zhao J, Rader DJ
Nat Med 2023 Mar;29(3):729-737. Epub 2023 Mar 6 doi: 10.1038/s41591-023-02222-w. PMID: 36879129Free PMC Article
Dib I, Khalil A, Chouaib R, El-Makhour Y, Noureddine H
Mol Biol Rep 2021 Jan;48(1):875-886. Epub 2021 Jan 3 doi: 10.1007/s11033-020-06071-5. PMID: 33389539Free PMC Article
Dron JS, Hegele RA
Front Endocrinol (Lausanne) 2020;11:455. Epub 2020 Jul 24 doi: 10.3389/fendo.2020.00455. PMID: 32793115Free PMC Article
Stroes E, Moulin P, Parhofer KG, Rebours V, Löhr JM, Averna M
Atheroscler Suppl 2017 Jan;23:1-7. Epub 2016 Dec 18 doi: 10.1016/j.atherosclerosissup.2016.10.002. PMID: 27998715
Gabcova-Balaziova D, Stanikova D, Vohnout B, Huckova M, Stanik J, Klimes I, Raslova K, Gasperikova D
Endocr Regul 2015 Jul;49(3):164-81. doi: 10.4149/endo_2015_03_164. PMID: 26238499

Recent systematic reviews

Ain Q, Cevc M, Marusic T, Sikonja J, Sadiq F, Sustar U, Mlinaric M, Kovac J, Batool H, Khan MI, Trebusak Podkrajsek K, Bizjan BJ, Battelino T, Fras Z, Ajmal M, Groselj U
Front Endocrinol (Lausanne) 2024;15:1387419. Epub 2024 Jun 7 doi: 10.3389/fendo.2024.1387419. PMID: 38911039Free PMC Article
Tripathi M, Wong A, Solomon V, Yassine HN
Endocr Pract 2021 Jan;27(1):71-76. Epub 2020 Nov 18 doi: 10.4158/EP-2020-0135. PMID: 33475504
Boudes PF
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