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Hyperlipidemia, familial combined, LPL related(FCHL3)

MedGen UID:
6965
Concept ID:
C0020474
Disease or Syndrome
Synonyms: FCHL3; Hyperapobetalipoproteinemia; Hyperlipidemia, familial combined
SNOMED CT: Familial combined hyperlipidemia (238040008); Familial multiple lipoprotein-type hyperlipidemia (299465007)
 
Gene (location): LPL (8p21.3)
 
HPO: HP:0008158
Monarch Initiative: MONDO:0007759
OMIM®: 144250

Definition

Familial combined hyperlipidemia (FCHL) is characterized by fluctuations in serum lipid concentrations and may present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B (APOB; 107730). Patients with FCHL are at increased risk of cardiovascular disease and mortality and have a high frequency of comorbidity with other metabolic conditions such as type 2 diabetes, nonalcoholic fatty liver disease, steatohepatitis, and the metabolic syndrome (summary by Bello-Chavolla et al., 2018). Goldstein et al. (1973) gave the designation 'familial combined hyperlipidemia' to the most common genetic form of hyperlipidemia identified in a study of survivors of myocardial infarction. Affected persons characteristically showed elevation of both cholesterol and triglycerides in the blood. The combined disorder was shown to be distinct from familial hypercholesterolemia (143890) and from familial hypertriglyceridemia (145750) for the following reasons: (1) lipid distributions in relatives were unique; (2) unlike familial hypercholesterolemia, children of affected persons did not express hypercholesterolemia; and (3) informative matings suggested that variable expression of a single gene rather than segregation for 2 separate genes was responsible. This disorder leads to elevated levels of VLDL, LDL, or both in plasma. From time to time the pattern can change in a given person. Unlike familial hypercholesterolemia, hyperlipidemia appears in only 10 to 20% of patients in childhood, usually in the form of hypertriglyceridemia. Xanthomas are rare. Increased production of VLDL may be a common underlying metabolic characteristic in this disorder, which may be heterogeneous. The disorder may be 5 times as frequent as familial hypercholesterolemia, occurring in 1% of the U.S. population. Genetic Heterogeneity of Susceptibility to Familial Combined Hyperlipidemia Also see FCHL1 (602491), associated with variation in the USF1 gene (191523) on chromosome 1q23, and FCHL2 (604499), mapped to chromosome 11. [from OMIM]

Clinical features

From HPO
Myocardial infarction
MedGen UID:
10150
Concept ID:
C0027051
Disease or Syndrome
Necrosis of the myocardium caused by an obstruction of the blood supply to the heart and often associated with chest pain, shortness of breath, palpitations, and anxiety as well as characteristic EKG findings and elevation of serum markers including creatine kinase-MB fraction and troponin.
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.
Increased LDL cholesterol concentration
MedGen UID:
154289
Concept ID:
C0549399
Finding
An elevated concentration of low-density lipoprotein cholesterol in the blood.
Increased VLDL cholesterol concentration
MedGen UID:
867364
Concept ID:
C4021729
Finding
An increase in the amount of very-low-density lipoprotein cholesterol in the blood.
Elevated circulating apolipoprotein B concentration
MedGen UID:
1632943
Concept ID:
C4703544
Finding
Increased circulating level of apolipoprotein B, which is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100.
Elevated circulating apolipoprotein A-II concentration
MedGen UID:
1638249
Concept ID:
C4703546
Finding
An increased concentration in blood of apolipoprotein A-II, a major component of HDL particles, associated with triglyceride and glucose metabolism.
Xanthelasma
MedGen UID:
56357
Concept ID:
C0155210
Disease or Syndrome
The presence of xanthomata in the skin of the eyelid.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyperlipidemia, familial combined, LPL related

Conditions with this feature

Sitosterolemia 1
MedGen UID:
440869
Concept ID:
C2749759
Disease or Syndrome
Sitosterolemia is characterized by: Hypercholesterolemia (especially in children) which (1) shows an unexpected significant lowering of plasma cholesterol level in response to low-fat diet modification or to bile acid sequestrant therapy; or (2) does not respond to statin therapy; Tendon xanthomas or tuberous (i.e., planar) xanthomas that can occur in childhood and in unusual locations (heels, knees, elbows, and buttocks); Premature atherosclerosis, which can lead to angina, aortic valve involvement, myocardial infarction, and sudden death; Hemolytic anemia, abnormally shaped erythrocytes (stomatocytes), and large platelets (macrothrombocytopenia). On occasion, the abnormal hematologic findings may be the initial presentation or the only clinical feature of this disorder. Arthritis, arthralgias, and splenomegaly may sometimes be seen and one study has concluded that "idiopathic" liver disease could be undiagnosed sitosterolemia. The clinical spectrum of sitosterolemia is probably not fully appreciated due to underdiagnosis and the fact that the phenotype in infants is likely to be highly dependent on diet.

Professional guidelines

PubMed

Yang Y, Mu Y, Zhao Y, Liu X, Zhao L, Wang J, Xie Y
J Genet Genomics 2007 May;34(5):381-91. doi: 10.1016/S1673-8527(07)60041-1. PMID: 17560523
Kwiterovich PO Jr
Pediatr Clin North Am 1990 Dec;37(6):1489-523. doi: 10.1016/s0031-3955(16)37021-3. PMID: 2259550

Recent clinical studies

Etiology

Suviolahti E, Lilja HE, Pajukanta P
Ann Med 2006;38(5):337-51. doi: 10.1080/07853890600865759. PMID: 16938803
Pajukanta P, Porkka KV, Antikainen M, Taskinen MR, Perola M, Murtomäki-Repo S, Ehnholm S, Nuotio I, Suurinkeroinen L, Lahdenkari AT, Syvänen AC, Viikari JS, Ehnholm C, Peltonen L
Arterioscler Thromb Vasc Biol 1997 May;17(5):841-50. doi: 10.1161/01.atv.17.5.841. PMID: 9157946
Marcil M, Boucher B, Gagné E, Davignon J, Hayden M, Genest J Jr
J Lipid Res 1996 Feb;37(2):309-19. PMID: 9026529
Babirak SP, Brown BG, Brunzell JD
Arterioscler Thromb 1992 Oct;12(10):1176-83. doi: 10.1161/01.atv.12.10.1176. PMID: 1390589
Kwiterovich PO Jr
Pediatr Clin North Am 1990 Dec;37(6):1489-523. doi: 10.1016/s0031-3955(16)37021-3. PMID: 2259550

Diagnosis

Minicocci I, Prisco C, Montali A, Di Costanzo A, Ceci F, Pigna G, Arca M
Atherosclerosis 2015 Oct;242(2):618-24. Epub 2015 Jun 18 doi: 10.1016/j.atherosclerosis.2015.06.036. PMID: 26342331
Pajukanta P, Porkka KV, Antikainen M, Taskinen MR, Perola M, Murtomäki-Repo S, Ehnholm S, Nuotio I, Suurinkeroinen L, Lahdenkari AT, Syvänen AC, Viikari JS, Ehnholm C, Peltonen L
Arterioscler Thromb Vasc Biol 1997 May;17(5):841-50. doi: 10.1161/01.atv.17.5.841. PMID: 9157946
Marcil M, Boucher B, Gagné E, Davignon J, Hayden M, Genest J Jr
J Lipid Res 1996 Feb;37(2):309-19. PMID: 9026529
Babirak SP, Brown BG, Brunzell JD
Arterioscler Thromb 1992 Oct;12(10):1176-83. doi: 10.1161/01.atv.12.10.1176. PMID: 1390589
Kwiterovich PO Jr
Pediatr Clin North Am 1990 Dec;37(6):1489-523. doi: 10.1016/s0031-3955(16)37021-3. PMID: 2259550

Therapy

Campagna F, Montali A, Baroni MG, Maria AT, Ricci G, Antonini R, Verna R, Arca M
Metabolism 2002 Oct;51(10):1298-305. doi: 10.1053/meta.2002.35197. PMID: 12370850

Prognosis

Minicocci I, Prisco C, Montali A, Di Costanzo A, Ceci F, Pigna G, Arca M
Atherosclerosis 2015 Oct;242(2):618-24. Epub 2015 Jun 18 doi: 10.1016/j.atherosclerosis.2015.06.036. PMID: 26342331
Vakkilainen J, Jauhiainen M, Ylitalo K, Nuotio IO, Viikari JS, Ehnholm C, Taskinen MR
J Lipid Res 2002 Apr;43(4):598-603. PMID: 11907142

Clinical prediction guides

Minicocci I, Prisco C, Montali A, Di Costanzo A, Ceci F, Pigna G, Arca M
Atherosclerosis 2015 Oct;242(2):618-24. Epub 2015 Jun 18 doi: 10.1016/j.atherosclerosis.2015.06.036. PMID: 26342331
Suviolahti E, Lilja HE, Pajukanta P
Ann Med 2006;38(5):337-51. doi: 10.1080/07853890600865759. PMID: 16938803
Campagna F, Montali A, Baroni MG, Maria AT, Ricci G, Antonini R, Verna R, Arca M
Metabolism 2002 Oct;51(10):1298-305. doi: 10.1053/meta.2002.35197. PMID: 12370850
Vakkilainen J, Jauhiainen M, Ylitalo K, Nuotio IO, Viikari JS, Ehnholm C, Taskinen MR
J Lipid Res 2002 Apr;43(4):598-603. PMID: 11907142
Hoffer MJ, Bredie SJ, Snieder H, Reymer PW, Demacker PN, Havekes LM, Boomsma DI, Stalenhoef AF, Frants RR, Kastelein JJ
Atherosclerosis 1998 May;138(1):91-9. doi: 10.1016/s0021-9150(98)00007-0. PMID: 9678774

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