Journal
EUROPEAN HEART JOURNAL
Volume 36, Issue 9, Pages 560-565Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehu058
Keywords
Homozygous; Autosomal dominant hypercholesterolemia; Familial hypercholesterolaemia; Prevalence; Phenotype
Categories
Funding
- Dutch Health Authority
- Dutch Heart Foundation [2006B190, 2006T102]
- Lifetime Achievement Award of the Dutch Heart Foundation [2010T082]
- Netherlands Organisation for Scientific Research [91612122]
Ask authors/readers for more resources
Aims Homozygous autosomal dominant hypercholesterolaemia (hoADH), an orphan disease caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9), is characterized by elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels and high risk for premature cardiovascular disease (CVD). The exact prevalence of molecularly defined hoADH is unknown. Therefore, we investigated the prevalence and phenotypical characteristics of this disease in an open society, i.e. the Netherlands. Methods and results The database of the nation wide ADH molecular diagnostic center was queried to identify all molecularly defined hoADH patients. Carriers of non-pathogenic mutations were excluded. Medical records were analysed for data regarding lipid levels and CVD events. Of 104 682 individuals screened for molecular defects, 49 were classified as hoADH (0.05%); 20 were true homozygotes, 25 were compound heterozygotes for LDLR mutations, and 4 were homozygous for APOB mutations. Nobi-allelic PCSK9 mutation carriers were identified. Consequently, the prevalence of hoADH was estimated to be similar to 1 : 300 000. Mean LDL-C levels prior to lipid-lowering treatment were 12.9 +/- 5.1 mmol/L (range 4.4-21.5 mmol/L). Surprisingly, only 50% of the patients met the clinical criteria for hoADH (LDL-C.13.0 mmol/L); 29% of patients suffered from a CVD event. Conclusion The prevalence of molecularly defined hoADH is much higher and the clinical phenotype is more variable than previously assumed. In light of the fact that novel therapies are, or will be registered for the treatment of hoADH patients, an uniform definition of hoADH either as a phenotypic or molecular entity is warranted in order to identify patients who are considered to be eligible for these novel agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available