Familial hypercholesterolemia (FH) is by definition one of the most common but often unrecognised fatal autosomal dominant monogenic diseases accounting for only 20% of diagnosed patients (1–3).There are two forms of familial hypercholesterolemia namely (5):
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The homozygous form is much rarer (1 in 1,000,000 cases). This homozygous form is associated with a very severe phenotypic expression with the occurrence of vascular accidents from adolescence. It’s very specific management is only carried out in a specialised environment.
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The heterozygous form is much more common, affecting 1/200 to 1/300 people. If one parent is affected, their children each have a 50% chance of being affected.
HF causes an increase in LDL-CT levels from birth. The atherosclerosis it causes begins in childhood and predisposes to premature coronary events in adulthood. For this reason, hypercholesterolemia that develops later in life is not suggestive of a familial form (1, 4).
The pathophysiology of HF is due to the presence of a single mutated allele (heterozygous state) of the LDLR genes, encoding the LDL receptor, APOB encoding apolipopotein B responsible for the binding between LDL particles and their receptor or PCSK9 encoding "Protein convertase subtilisin/kexin type 9" which facilitates the lysosomal degradation of the LDL receptor)(6). A single mutated allele contributes to a 50% reduction in hepatic clearance of LDL lipoproteins, resulting in LDL cholesterol (LDL-C) levels that are twice as high as normal levels since birth.
The diagnosis of HF is based on a triad of MedPed scores combining (1, 7):
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History:
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Family history :
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First-degree relative with premature coronary or vascular disease (male < 55 years, female < 60 years) (1)
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First-degree relative with LDL-c > 95th percentile (1)
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First-degree relative with tendon xanthomas and/or corneal arc (2)
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Child < 18 years with LDL-c > 95th percentile (2)
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Personal
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Premature coronary disease (male < 55 years, female < 60 years) (2)
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Premature cerebral or lower limb arterial occlusive disease premature(1)
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Clinical signs
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Biological data
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Biochemical :
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LDL-c > 3.30 g/l (> 8.5 mmol/l) (8)
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LDL-c: 2.50–3.29 g/l (6.5–8.4 mmol/l) (5)
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LDL-c: 1.90–2.49 g/l (5.0-6.4 mmol/l) (3)
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LDL-c:1.55–1.89 g/l (4.0-4.9 mmol/l) (1)
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DNA analysis
The MedPed score is classified into three:
In our case, our patient had a high MedPed score of 12 based on history, clinic and biochemistry only. A confirmation was performed,
Objectivating a copy of the LDL-Receptor gene. Family screening must be done early once the diagnosis is evoked because complications are early. In our case the notion of hypercholesterolemia was objectified in the brother and the mother with complications such as MI and DVA.
In children and adolescents from the age of 8 to 10 years, when the LDL-c level remains above 1.9 g/l after a period of at least 6 months of dietary hygiene measures (1). It is now recommended that a statin be chosen as first-line treatment in children and adolescents, as in adults, but at the lowest effective dose (3, 8). They are thus the most important class of drugs for reducing LDL-c. Several molecules are marketed, which allow a reduction in LDL-c of 30 to 50% to be achieved. The latter depends on both the molecule chosen and the dose used. (1) In practice, given the significant rise in LDL-c, it is most often necessary to use the most potent statins, in particular atorvastatin or rosuvastatin. Ezetimibe, on the other hand, allows an average reduction in LDL-c of around 20%, as do anti-PCSK9 antibodies.
In our case, the patient received a high dose of statin and ezetimibe from the start.