Familial combined hyperlipidemia is an autosomal inherited lipid abnormality and one of the most common genetic dyslipidemias, whose features partly overlap with those of the metabolic syndrome. This condition is characterized by high levels of total cholesterol and triglycerides, decreased high density lipoprotein (HDL) cholesterol concentration, high apoB concentration, and high low density lipoprotein (LDL) levels. Patients are usually asymptomatic during childhood, although biochemical abnormalities are present at a young age, but have significant cardiovascular disease as they grow older.
Familial combined hyperlidemia patients are initially asymptomatic, but need to monitor body weight  and waist- to- hip ratio  in order to avoid abdominal obesity, that seems to be related to lipid profile modification. These parameters are also in relation with other biochemical abnormalities: decreased leptin and adiponectin  and high insulin resistance . Same principles apply to children who come from affected parents, who need to maintain body weight within normal range.
Signs of hepatic suffering may be encountered in the context of fatty liver and non-alcoholic steatohepatitis , but they are not specific for familial combined hyperlidemia. Clinical examination is noncontributory in some cases, because xanthoma are almost never present in this disease .
Patients may also suffer form arterial hypertension , which further increases cardiovascular risk.
Entire Body System
- Coronary Atherosclerosis
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The biochemical profile has several specific traits: reduced HDL level (<40 mg/dL), high LDL level (> 160 mg/dL) and/or high triglyceride (TG) level (> 200 mg/dL). High LDL and TG levels (in association) are usually not found in the general population, only one of them is usually present. These parameters must be evaluated in a recurrent manner, keeping in mind that members of the same family may have different phenotypes . Familial combined hyperlidemia is also characterized by increased apo B levels (> 125 mg/dL), which also constitutes a good prognostic factor .
Vascular echography is used to measure carotid artery intima-media thickness, which is increased in patients that already had a cardiovascular or cerebrovascular event. Other echography findings, like increased pulse wave velocity and reduced flow mediated dilation are reliable parameters that assess endothelial dysfunction and arterial stiffness, but are unable to increase event prediction . Ultrasound analysis should not be limited to carotid arteries, it should also be performed on femoral arteries and the aorta. Silent myocardial ischemia should also be taken into consideration and evaluated using stress tests. Echography of the heart and the aorta should be performed every year. Computed-tomography coronary angiography is also an option in uncertain cases. Carotid intima medial thickness should also be assessed in children. They can also benefit from positron emission tomography scans in selected cases because if significant plaque is present, hypolipemic treatment may be initialized by a pediatric cardiologist.
Genetic studies reveal a locus on chromosome 1 (1q21-q23) that is linked both to familial combined hyperlidemia and type 2 diabetes . Apo AV gene may also be linked to disease transmission , as well as the gene encoding upstream transcription factor 1 . However, gene expression depends on environmental factors, making the diagnosis even more difficult .
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