hyperlipoproteinemia type 2 (familial hypercholesterolemia)
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Etiology
- primary: defect in LDL receptor
- secondary increases in LDL
Epidemiology
- gene frequency 0.2-0.5% in USA, but as high as 1.3% in white South Africans & in Lebanon
Pathology
- receptor defect impairs the catabolism of LDL, & the resultantelevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), & coronary arteries (atherosclerosis)
Genetics
- autosomal dominant form
- genetic variation in GHR may act as phenotype modifier in familial hypercholesterolemia patients carrying a mutation in the LDLR gene
- APOB, PCSK9, & LDLRAP1 may also play a role[5]
Clinical manifestations
- cutaneous xanthomas before 10 years of age for homozygous familial hypercholesterolemia
- corneal arcus
- premature atherosclerosis
Laboratory
- increased serum cholesterol & LDL cholesterol
- untreated LDL cholesterol > 500 mg/dL (before 10 years of age for homozygous familial hypercholesterolemia[5]
- genetic testing
Radiology
- echocardiogram & evaluation of aorta annually
- CT coronary angiography every 5 years or more frequently accounting for severity of disease & radiation exposure[5]
Complications
- 10% with myocardial infarction at a young age[7]
Management
- diet is the foundation of treatment
- weight loss
- AHA diet step 1 or step 2
- maximum diet affect is observed in 4-5 weeks
- more frequent eating may reduce serum cholesterol & LDL cholesterol[3] {6-10 mg/dL decrease for cholesterol}
- pharmaceutical agents
- HMG CoA reductase inhibitors (statins)
- statins for children improve LDL cholesterol & reduce risk of cardiovascular events in adulthood[8]
- mean LDL cholesterol achieved 161 mg/dL (untreated 237 mg/dL)[8]
- lomitapide (Juxtapid)[5]
- mipomersen (Kynamro)[5]
- bile acid sequestrants, niacin & fibrates not recommended[5]
- HMG CoA reductase inhibitors (statins)
- apheresis with selective LDL cholesterol removal[4]
- begin 5-8 years of age
- target LDL cholesterol
- < 100 mg/dL (adults)
- < 70 mg/dL (adults with cardiovascular disease)
- < 135 mg/dL (children)[5]
- no benefit in screening for dyslipidemia children or adolescents[6]
More general terms
More specific terms
Additional terms
- bile acid sequestrant
- fibrate
- HMG CoA reductase inhibitor (statin)
- low-density lipoprotein receptor; LDL receptor; apoB/E receptor (LDLR)
- National Cholesterol Education Program (NCEP) step 1 diet
- nicotinic acid (niacin, vitamin B3, Niaspan)
References
- ↑ Clinical Diagnosis & Management by Laboratory Methods, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1991, pg 208
- ↑ Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1038
- ↑ 3.0 3.1 Journal Watch 22(3):21, 2002 Titan SM et al Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study. BMJ. 2001 Dec 1;323(7324):1286-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11731392
- ↑ 4.0 4.1 Medical Knowledge Self Assessment Program (MKSAP) 16, 18. American College of Physicians, Philadelphia 2012, 2018.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Anello J, Feinberg B, Heinegg J, Lindsey R, Wojdylo C, Wong O. Medcsape Oncology. August 2014 Guidelines on homozygous familial hypercholesterolemia (HoFH) from the European Atherosclerosis Society http://reference.medscape.com/features/slideshow/guidelines-review/august2014
- ↑ 6.0 6.1 Lozano P, Henrikson NB, Dunn J et al Lipid Screening in Childhood and Adolescence for Detection of Familial Hypercholesterolemia. Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016;316(6):645-655 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27532919 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2542641
- ↑ 7.0 7.1 Singh A, Gupta A, Collins BL et al. Familial hypercholesterolemia among young adults with myocardial infarction. J Am Coll Cardiol 2019 May 21; 73:2439. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31097165 https://www.sciencedirect.com/science/article/pii/S0735109719345528
- ↑ 8.0 8.1 8.2 Luirink IK, Wiegman A, Kusters DM et al. 20-year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med 2019 Oct 17; 381:1547-1556 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31618540 https://www.nejm.org/doi/10.1056/NEJMoa1816454
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hyperlipoproteinemia type 2 (familial hypercholesterolemia) patient information