Autosomal dominant familial dysbetalipoproteinemia: A pathophysiological framework and practical approach to diagnosis and therapy
Open accessAbstract
Familial dysbetalipoproteinemia (FD) is a genetic disorder of lipoprotein metabolism associated with an increased risk for premature cardiovascular disease. In about 10% of the cases, FD is caused by autosomal dominant mutations in the apolipoprotein E gene (APOE). This review article provides a pathophysiological framework for autosomal dominant FD (ADFD) and discusses diagnostic challenges and therapeutic options. The clinical presentation and diagnostic work-up of ADFD are illustrated by two cases: a male with premature coronary artery disease and a p.K164Q mutation in APOE and a female with mixed hyperlipidemia and a p.R154H mutation in APOE. ADFD is characterized by a fasting and postprandial mixed hyperlipidemia due to increased remnants. Remnants are hepatically cleared by the low-density lipoprotein receptor and the heparan sulfate proteoglycan receptor (HSPG-R). Development of FD is associated with secondary factors like insulin resistance that lead to HSPG-R degradation through sulfatase 2 activation. Diagnostic challenges in ADFD are related to the clinical presentation; lipid phenotype; dominant inheritance pattern; genotyping; and possible misdiagnosis as familial hypercholesterolemia. FD patients respond well to lifestyle changes and to combination therapy with statins and fibrates. To conclude, diagnosing ADFD is important to adequately treat patients and their family members. In patients presenting with mixed hyperlipidemia, (autosomal dominant) FD should be c…
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About 10% of FD patients have rare APOE variants associated with autosomal dominant FD.
“About 10% of FD patients have rare APOE variants associated with autosomal dominant FD.”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [28]
APOE3-Ch is a rare genetic variant of APOE and has been associated with HLPP3 in patients.
“APOE3‐Ch is a rare genetic variant of APOE and has been associated with HLPP3 in patients. 21”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [21]
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- Authors
- Koopal, C., Marais, A. D., Westerink, J., & Visseren, F. L. J.
- Affiliations
- University Medical Center Utrecht (NL)
- University of Cape Town (ZA)
- Corresponding author
- Visseren, Frank L.J.
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 11
- Issue
- 1
- Pages
- 12-23.e1
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W2531311132
- Cited by
- 53
- References
- 14
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- Journal of clinical lipidology (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- University of Cape Town
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- apolipoprotein E, mixed dyslipidemia, remnant lipoproteins, LDL receptor, SULF2, insulin resistance, premature coronary artery disease, statins, fibrates, genetic diagnosis
- MeSH terms
- Genotype, Humans, Hyperlipoproteinemia Type III, Phenotype, Heparan Sulfate Proteoglycans
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