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Hyperlipidemia due to hepatic triglyceride lipase deficiency

MedGen UID:
462816
Concept ID:
C3151466
Disease or Syndrome
Synonyms: Hepatic lipase deficiency; LIPC DEFICIENCY
SNOMED CT: Hepatic lipase deficiency (720940008); Hyperlipidemia due to hepatic triglyceride lipase deficiency (720940008)
 
Gene (location): LIPC (15q21.3)
 
Monarch Initiative: MONDO:0013533
OMIM®: 614025
Orphanet: ORPHA140905

Definition

Hepatic lipase deficiency is characterized by premature atherosclerosis, elevated total cholesterol, triglycerides (TG), and very low density lipoprotein (VLDL), as well as TG-rich low density lipoprotein (LDL) and HDL subfractions (summary by Hegele et al., 1991). [from OMIM]

Additional description

From MedlinePlus Genetics
Hepatic lipase deficiency is a disorder that affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of certain fats, known as triglycerides and cholesterol, in the blood. These individuals also have increased amounts of molecules known as high-density lipoproteins (HDLs) and decreased amounts of molecules called low-density lipoproteins (LDL). These molecules transport triglycerides and cholesterol throughout the body. In people with hepatic lipase deficiency, the LDL molecules are often abnormally large.

Normally, high levels of HDL (known as "good cholesterol") and low levels of LDL (known as "bad cholesterol") are protective against an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease. However, some individuals with hepatic lipase deficiency, who have this imbalance of HDL and LDL, develop atherosclerosis and heart disease in mid-adulthood, while others do not. It is unknown whether people with hepatic lipase deficiency have a greater risk of developing atherosclerosis or heart disease than individuals in the general population. Similarly, it is unclear how increased blood triglycerides and cholesterol levels affect the risk of atherosclerosis and heart disease in people with hepatic lipase deficiency.  https://medlineplus.gov/genetics/condition/hepatic-lipase-deficiency

Clinical features

From HPO
Angina pectoris
MedGen UID:
1929
Concept ID:
C0002962
Sign or Symptom
Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia.
Hypercholesterolemia
MedGen UID:
5687
Concept ID:
C0020443
Disease or Syndrome
An increased concentration of cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Increased HDL cholesterol concentration
MedGen UID:
1636134
Concept ID:
C4551591
Finding
An elevated concentration of high-density lipoprotein cholesterol (HDL) in the blood.
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.
Arcus senilis
MedGen UID:
8179
Concept ID:
C0003742
Finding
A hazy, grayish-white ring about 2 mm in width located close to but separated from the limbus (the corneoscleral junction). Corneal arcus generally occurs bilaterally, and is related to lipid deposition in the cornea. Corneal arcus can occur in elderly persons as a part of the aging process but may be associated with hypercholesterolemia in people under the age of 50 years.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyperlipidemia due to hepatic triglyceride lipase deficiency

Professional guidelines

PubMed

Pritchard AB, Strong A, Ficicioglu C
Orphanet J Rare Dis 2020 Feb 24;15(1):58. doi: 10.1186/s13023-020-1328-6. PMID: 32093730Free PMC Article
Watts GF, Ooi EM, Chan DC
Nat Rev Cardiol 2013 Nov;10(11):648-61. Epub 2013 Sep 24 doi: 10.1038/nrcardio.2013.140. PMID: 24060958
Hegele RA, Little JA, Connelly PW
Atherosclerosis 1999 Mar;143(1):219-22. doi: 10.1016/s0021-9150(98)00266-4. PMID: 10208500

Recent clinical studies

Etiology

Fang Z, Shen G, Wang Y, Hong F, Tang X, Zeng Y, Zhang T, Liu H, Li Y, Wang J, Zhang J, Gao A, Qi W, Yang X, Zhou T, Gao G
Signal Transduct Target Ther 2024 Mar 12;9(1):66. doi: 10.1038/s41392-024-01781-9. PMID: 38472195Free PMC Article
Basu D, Bornfeldt KE
Front Endocrinol (Lausanne) 2020;11:504. Epub 2020 Aug 6 doi: 10.3389/fendo.2020.00504. PMID: 32849290Free PMC Article
Pritchard AB, Strong A, Ficicioglu C
Orphanet J Rare Dis 2020 Feb 24;15(1):58. doi: 10.1186/s13023-020-1328-6. PMID: 32093730Free PMC Article
Watts GF, Ooi EM, Chan DC
Nat Rev Cardiol 2013 Nov;10(11):648-61. Epub 2013 Sep 24 doi: 10.1038/nrcardio.2013.140. PMID: 24060958
Bishop JR, Stanford KI, Esko JD
Curr Opin Lipidol 2008 Jun;19(3):307-13. doi: 10.1097/MOL.0b013e3282feec2d. PMID: 18460924

Diagnosis

Lightbourne M, Startzell M, Bruce KD, Brite B, Muniyappa R, Skarulis M, Shamburek R, Gharib AM, Ouwerkerk R, Walter M, Eckel RH, Brown RJ
J Clin Lipidol 2022 Nov-Dec;16(6):850-862. Epub 2022 Sep 22 doi: 10.1016/j.jacl.2022.06.011. PMID: 36195542Free PMC Article
Maciejko JJ, Anne P, Raza S, Lyons HJ
J Clin Lipidol 2017 Mar-Apr;11(2):567-574. Epub 2017 Feb 22 doi: 10.1016/j.jacl.2017.02.006. PMID: 28502515
Laurila PP, Soronen J, Kooijman S, Forsström S, Boon MR, Surakka I, Kaiharju E, Coomans CP, Van Den Berg SA, Autio A, Sarin AP, Kettunen J, Tikkanen E, Manninen T, Metso J, Silvennoinen R, Merikanto K, Ruuth M, Perttilä J, Mäkelä A, Isomi A, Tuomainen AM, Tikka A, Ramadan UA, Seppälä I, Lehtimäki T, Eriksson J, Havulinna A, Jula A, Karhunen PJ, Salomaa V, Perola M, Ehnholm C, Lee-Rueckert M, Van Eck M, Roivainen A, Taskinen MR, Peltonen L, Mervaala E, Jalanko A, Hohtola E, Olkkonen VM, Ripatti S, Kovanen PT, Rensen PC, Suomalainen A, Jauhiainen M
Sci Transl Med 2016 Jan 27;8(323):323ra13. doi: 10.1126/scitranslmed.aad0015. PMID: 26819196
Watts GF, Ooi EM, Chan DC
Nat Rev Cardiol 2013 Nov;10(11):648-61. Epub 2013 Sep 24 doi: 10.1038/nrcardio.2013.140. PMID: 24060958
Sabesin SM, Bertram PD, Freeman MR
Adv Intern Med 1980;25:117-46. PMID: 6987838

Therapy

Lightbourne M, Startzell M, Bruce KD, Brite B, Muniyappa R, Skarulis M, Shamburek R, Gharib AM, Ouwerkerk R, Walter M, Eckel RH, Brown RJ
J Clin Lipidol 2022 Nov-Dec;16(6):850-862. Epub 2022 Sep 22 doi: 10.1016/j.jacl.2022.06.011. PMID: 36195542Free PMC Article
Pritchard AB, Strong A, Ficicioglu C
Orphanet J Rare Dis 2020 Feb 24;15(1):58. doi: 10.1186/s13023-020-1328-6. PMID: 32093730Free PMC Article
Goldberg IJ
Arterioscler Thromb Vasc Biol 2018 Apr;38(4):700-706. Epub 2018 Feb 1 doi: 10.1161/ATVBAHA.117.309666. PMID: 29419410Free PMC Article
Watts GF, Ooi EM, Chan DC
Nat Rev Cardiol 2013 Nov;10(11):648-61. Epub 2013 Sep 24 doi: 10.1038/nrcardio.2013.140. PMID: 24060958
Hegele RA
Atheroscler Suppl 2002 Mar;2(3):5-7. doi: 10.1016/s1567-5688(01)00013-7. PMID: 11923122

Prognosis

Dergunov AD, Hoy A, Smirnova EA, Visvikis S, Siest G
Int J Biochem Cell Biol 2003 Apr;35(4):530-43. doi: 10.1016/s1357-2725(02)00359-x. PMID: 12565713
Faustinella F, Chang A, Van Biervliet JP, Rosseneu M, Vinaimont N, Smith LC, Chen SH, Chan L
J Biol Chem 1991 Aug 5;266(22):14418-24. PMID: 1907278
Wanner C, Frommherz K, Hörl WH
Cardiology 1991;78(3):202-17. doi: 10.1159/000174787. PMID: 1868498
Pelkonen R, Nikkilä EA, Grahne B
Clin Endocrinol (Oxf) 1982 Apr;16(4):383-90. doi: 10.1111/j.1365-2265.1982.tb00731.x. PMID: 7047001
Sabesin SM, Bertram PD, Freeman MR
Adv Intern Med 1980;25:117-46. PMID: 6987838

Clinical prediction guides

Yuan C, Xu Y, Lu G, Hu Y, Mao W, Ke L, Tong Z, Xia Y, Ma S, Dong X, Xian X, Wu X, Liu G, Li B, Li W
Mol Ther 2024 Jan 3;32(1):59-73. Epub 2023 Nov 15 doi: 10.1016/j.ymthe.2023.11.018. PMID: 37974401Free PMC Article
Pasta A, Borro P, Cremonini AL, Formisano E, Tozzi G, Cecchi S, Fresa R, Labanca S, Djahandideh A, Sukkar SG, Picciotto A, Pisciotta L
Pharmacol Res Perspect 2021 Oct;9(5):e00820. doi: 10.1002/prp2.820. PMID: 34476902Free PMC Article
Stanford KI, Wang L, Castagnola J, Song D, Bishop JR, Brown JR, Lawrence R, Bai X, Habuchi H, Tanaka M, Cardoso WV, Kimata K, Esko JD
J Biol Chem 2010 Jan 1;285(1):286-94. Epub 2009 Nov 4 doi: 10.1074/jbc.M109.063701. PMID: 19889634Free PMC Article
Hegele RA
Atheroscler Suppl 2002 Mar;2(3):5-7. doi: 10.1016/s1567-5688(01)00013-7. PMID: 11923122
Connelly PW, Maguire GF, Lee M, Little JA
Arteriosclerosis 1990 Jan-Feb;10(1):40-8. doi: 10.1161/01.atv.10.1.40. PMID: 2297346

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