To characterize the dyslipidemias and their consequences in carriers of mutations in glycosylation genes.
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Correlation between genetic glycosylation defects and lipid profile.
Secondary outcome
- Correlation between genetic glycosylation defects and postprandial
triglyceride clearance
- Correlation between genetic glycosylation defects and fat percentage found
at 1H-MR spectroscopy of the liver.
- Difference between vessel wall dimensions (total wall volume, mean wall area,
mean wall thickness, normalized walll index measured by MRI), wall shear stress
(measured by MRI) between subjects with genetic defects in glycosylation and
healthy non-affected family members or healthy control subjects
Background summary
Dyslipidemia is a major driver of atherosclerotic cardiovascular disease (CVD),
the leading cause of death worldwide.Recently, we identified an entirely new
group of dyslipidemias: those caused by defective glycosylation of proteins
involved in lipid metabolism.
Our studies have identified a variety of aberrant lipid profiles in CDG
patients. For example, we found severe hypocholesterolemia and
hypobetalipoproteinemia in a series of nineteen type 1 CDG patients.
Given the severe phenotype in CDG patients generally including mental
retardation, it is not possible to study whether the dyslipidemias observed in
these patients affect postprandial lipid profiles, hepatic lipid storage and
the development of atherosclerotic cardiovascular disease. Yet such studies are
feasible in heterozygous family members of these patients, who do not display a
severe phenotype, are otherwise healthy, but in whom alterations in plasma
cholesterol concentrations have been reported (OMIM #601785). Furthermore, a
pilot study of six obligate heterozygous parents of patients with ALG6-CDG
showed the same phenotype as in the CDG patients: extremely low values for
total cholesterol and low-density lipoprotein (LDL) cholesterol (below the 5th
percentile for age and gender) and low apolipoprotein B.
Study objective
To characterize the dyslipidemias and their consequences in carriers of
mutations in glycosylation genes.
Study design
This study will focus on (pre- en postprandial) cholesterol profiles, hepatic
lipid storage and atherosclerosis in individuals with genetic defects of
glycosylation and their family members. The results obtained in genetically
affected subjects are compared with non-affected family members that are
matched for relevant parameters. If an insufficient number of non-affected
relatives volunteer, we will complement the control group with unrelated
matched controls recruited by advertisement.
Study burden and risks
The risks involved with participating in this study are estimated to be low
with blood withdrawal and imaging without radiotion exposure (MRI) being the
main study methods.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Included are all healthy heterozygous carriers and non-affected family members of patients diagnosed with congenital disorder of glycosylation, aged 18 or older. Healthy individuals will be included as a control population.
Exclusion criteria
- Known systemic disorders such as hepatic, renal, hematologic, and malignant
diseases or any clinically significant medical condition that could interfere with the
conduct of the study in the opinion of the investigator.
- Standard contra-indications to MRI based on physicians experience and current practices
- Claustrophobia
- Metal in the body, as a result of e.g. osteosynthetic material, pacemaker
implantation or artificial cardiac valves.
- Inability or unwillingness to comply with the protocol requirements.;When dyslipidemia is present, exclusion criteria are all secondary causes of dyslipidemia (nephrotic syndrome, adrenal insufficiency, renal insufficiency, hypothyroidism, heavy alcohol use, cholestasis, use of protease inhibitors).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL46676.018.13 |