Autosomal recessive hypercholesterolemia in Spain

Toward a new clinical classification of patients with familial hypercholesterolemia: One perspective from Spain

“…These patients have both LDLR adaptor protein 1 (LDLRAP1) gene alleles affected. The severity of the illness falls between the other HoFH forms, and a better response to statins has been observed [9].…”

Autosomal recessive hypercholesterolemia: Case report

“…9 S anchez-Hern andez et al have suggested that some heterozygous LDLRAP1 mutations may contribute to polygenic hypercholesterolemia. 1 The homozygosity of this novel, extremely rare variant raises the suspicion regarding any possible consanguinity or uniparental disomy (of the first chromosome, in this case). Any close familial relationships between the parents of the patient were ruled out during the genetic counseling of the patient, when a three-generation genealogy was analyzed.…”

“…Autosomal recessive hypercholesterolemia (ARH) (OMIM #603813) is a very rare monogenic disorder affecting less than 1:1000,000 of the population and is characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), leading to aggressive and premature atherosclerotic cardiovascular disease (CVD). 1 ARH is caused by pathogenic variants in the LDL receptor adaptor protein 1 (LDLRAP1) gene, resulting in a truncated or nonfunctional adaptor protein that is involved in the uptake in the LDL receptor (LDLR) and clearance of LDL particles. 1 Homozygous or compound heterozygous pathogenic variants in other genes, such as apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), or the LDLR gene, are found in patients with homozygous familial hypercholesterolemia (HoFH), demonstrating a clinical phenotype consistent with ARH 2 -extremely high LDL-C levels, very extensive cutaneous or tendon xanthomas, aortic stenosis, and premature atherosclerotic CVD.…”

“…1 Homozygous or compound heterozygous pathogenic variants in other genes, such as apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), or the LDLR gene, are found in patients with homozygous familial hypercholesterolemia (HoFH), demonstrating a clinical phenotype consistent with ARH 2 -extremely high LDL-C levels, very extensive cutaneous or tendon xanthomas, aortic stenosis, and premature atherosclerotic CVD. 1,2 However, owing to currently unknown reasons, patients with HoFH have a greatly reduced life expectancy, higher rates of premature atherosclerotic CVD (including risks of myocardial infarction before the age of 20 years), and an even worse response to lipid-lowering treatment compared to patients with ARH. [1][2][3][4][5] The prevalence of FH is commonly reported as 1 in 500 individuals.…”

“…1,2 However, owing to currently unknown reasons, patients with HoFH have a greatly reduced life expectancy, higher rates of premature atherosclerotic CVD (including risks of myocardial infarction before the age of 20 years), and an even worse response to lipid-lowering treatment compared to patients with ARH. [1][2][3][4][5] The prevalence of FH is commonly reported as 1 in 500 individuals. 6 Recent studies showed the prevalence of heterozygous FH consistent with the ratios of 1:200-1:250; by extrapolation, HoFH may affect up to 6 individuals per million (or 1 in 160,000-300,000).…”