Journal of Inherited Metabolic Disease

, Volume 30, Issue 2, pp 239–247 | Cite as

Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations

  • K. Widhalm
  • A. Dirisamer
  • A. Lindemayr
  • G. Kostner
Original Article


Background: One major problem of using hypercholesterolaemia alone as a primary criterion for diagnosing familial hypercholesterolaemia (FH) is that 15–40% of relatives may be misdiagnosed because plasma lipid levels in FH heterozygotes overlap with those in the general population. Setting: General Hospital/University of Vienna, Department of Pediatrics, Outpatient lipid clinic. Methods: As a part of the MED-PED (make early diagnosis – prevent early death) project we are currently investigating children, adolescents and their relatives who are suspected to be affected with FH in our out-patient clinic for metabolic diseases using MED-PED inclusion criteria and confirming the diagnosis by means of DNA analysis. Patients: 263 patients with premature atherosclerosis and/or hypercholesterolaemia: 116 children (mean age 11.6 ± 4.1 years; 57 girls and 59 boys) and 147 adults (64 women, mean age 41.5 ± 13.7 years; 83 men, mean age 42.8 ± 10.8 years). Results: 119 patients with mutations have been detected; 56 children with either low density lipoprotein receptor (LDLR) and/or ApoB mutations (27 girls and 29 boys; mean total cholesterol (TC) 275 ± 71 mg/dl, triglycerides (TG) 101 ± 57 mg/dl, high-density lipoprotein cholesterol (HDL-C) 49 ± 12 mg/dl, low-density lipoprotein cholesterol (LDL-C) 198 ± 67 mg/dl) and one boy with a homozygous. LDLR mutation. A further 62 adults with LDLR and/or ApoB mutations were documented; 33 women (mean age 36.9 ± 11.1 years; mean TC 283 ± 76 mg/dl, TG 137 ± 78 mg/dl, HDL-C 55 ± 17 mg/dl, LDL-C 210 ± 67 mg/dl) and 29 men (mean age 45.0 ± 10.6 years; mean TC 301 ± 87 mg/dl, TG 163 ± 112 mg/dl, HDL-C 42 ± 12 mg/dl, LDL-C 233 ± 83 mg/dl). In 32 of these subjects (11 children (21%), 21 adults (42%)), serum lipid levels were lower than the diagnostic MED-PED limits adopted, so that they might have been misclassified without an additional DNA analysis. Conclusion: In our study, diagnosis of FH and related disorders (ApoB-100 defect) by means of conventional laboratory methods missed at least 21% in children and 42% in adults affected with LDLR and/or ApoB gene mutations. Genetic FH diagnosis provides a tool for specific diagnosis of mutation carrier status.


Familial Hypercholesterolemia Serum Lipid Level Arterioscler Thromb Vasc Biol Familial Hypercholesterolemia Familial Hypercholesterolaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



coronary heart disease


familial hypercholesterolaemia


high-density lipoprotein cholesterol


low-density lipoprotein cholesterol


low density lipoprotein receptor


myocardial infarction


make early diagnosis – prevent early death


total cholesterol




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Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • K. Widhalm
    • 1
  • A. Dirisamer
    • 1
    • 2
  • A. Lindemayr
    • 1
  • G. Kostner
    • 3
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Department of RadiologyUniversity of ViennaViennaAustria
  3. 3.Department of Medical BiochemistryUniversity of GrazGrazAustria

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