Autosomal Recessive Hypercholesterolemia: A Mild Phenotype of Familial Hypercholesterolemia: Insight from the Kinetic Study using Stable Isotope and Animal Studies

Tada, Hayato; Kawashiri, Masa‐aki; Nohara, Atsushi; Inazu, Akihiro; Kobayashi, Junji; Mabuchi, Hiroshi; Yamagishi, Masakazu

doi:10.5551/jat.27227

Cited by 21 publications

(18 citation statements)

References 48 publications

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“…7 A very mild, extremely rare form of FH caused by mutations in LDLRAP1, the gene encoding for LDLR adaptor protein 1, is named autosomal recessive hypercholesterolaemia. 8,9 Genetic criteria Genomic tests to identify mutations in LDLR, APOB, or PCSK9 are available, although their use varies considerably between countries. For example, this approach is more used in Europe-especially in the Netherlands, Norway, Czech Republic, and Iceland-than in the USA.…”

Section: Diagnosismentioning

confidence: 99%

Management of patients with familial hypercholesterolaemia

Reiner

2015

Nat Rev Cardiol

101

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Familial hypercholesterolaemia (FH) is an autosomal inherited disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels and an increased risk of premature atherosclerotic cardiovascular disease. Although FH is one of the most common genetic disorders, this disorder remains mostly undetected and its management is often suboptimal. High-intensity statins are standard treatment for patients with FH, but LDL-C levels in most patients treated with statin monotherapy remain above those recommended by guidelines. Combination therapy to lower LDL-C levels further-such as treatment with statins plus ezetimibe-has been successful, and combination of apheresis with high-intensity statin treatment is used in patients with homozygous FH and in those with heterozygous FH who are statin-refractory. Mipomersen, an inhibitor of apolipoprotein B-100 synthesis, and lomitapide, a microsomal triglyceride transfer protein inhibitor, reduce LDL-C levels further when added to high-intensity statin treatment in homozygous FH, but both have important adverse effects, such as increasing liver fat content. At present, PCSK9 inhibition (with alirocumab or evolocumab) is well tolerated and reduces LDL-C levels considerably in patients receiving the maximally tolerated statin treatment, and seems the most promising emerging treatment option. Nevertheless, data from outcome trials with hard end points for PCSK9 inhibitors, mipomersen, and lomitapide are still needed before these therapies become standard for patients with FH.

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Section: Diagnosismentioning

confidence: 99%

Management of patients with familial hypercholesterolaemia

Reiner

2015

Nat Rev Cardiol

101

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“…3,4 Additionally, recessive autosomal FH has been described, involving mutations on both LDLRAP1 alleles (<1% of cases; OMIM #695747). 5 The recessive form of FH is clinically indistinguishable from HoFH, [6][7][8] although less aggressive phenotypes have also been described, 9 for this reason, this form of FH has also been included in our studies. The classical HoFH prevalence is 1:1 000 000, 1 with higher rates in genetically isolated populations, such as French Canadians, Afrikaners from South Africa, or Christian Lebanese people.…”

mentioning

confidence: 99%

Homozygous Familial Hypercholesterolemia in Spain

Sánchez-Hernández¹,

Civeira²,

Stef³

et al. 2016

Circ Cardiovasc Genet

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Recent genetic studies of FH highlight the great variability of the clinical phenotypes in HoFH and heterozygous FH (HeFH), the poor genotype-phenotype correlation, and the large clinical overlap between HoFH and HeFH. 15,[18][19][20] These findings can be explained based on the variations in the number of genes involved, the specific pathogenic mutations, and Background-Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL protein receptor adaptor 1 (LDLRAP1

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“…Some patients have 3-fold higher serum cholesterol levels than others, and their levels are not significantly different from those of classic FH homozygotes [7]. In some patients with ARH, large tuberous, tendinous or planar xanthomas are present, which are occasionally accompanied by corneal arcus and xanthelasmas [3,7].…”

Section: Clinical Phenotype Of Patients With Arhmentioning

confidence: 95%

“…Only 36 families with 14 different mutations have been reported in the literature until recently [3]. However, in some regions the prevalence of ARH appears to be higher and in the island of Sardinia the frequency of a heterozygous carrier mutation status for the LDLRAP1 gene is estimated to be approximately 1:143 individuals [3].…”

Section: Introductionmentioning

confidence: 99%

“…As it was mentioned above, ARH is extremely rare with no more than 10,000 cases alive up to date, which are mostly found in the Lebanese, Mexican, Japanese, Indian, Turkish, Syrian and Italian populations [2]. Only 36 families with 14 different mutations have been reported in the literature until recently [3]. However, in some regions the prevalence of ARH appears to be higher and in the island of Sardinia the frequency of a heterozygous carrier mutation status for the LDLRAP1 gene is estimated to be approximately 1:143 individuals [3].…”

Section: Introductionmentioning

confidence: 99%

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