Homozygous Familial Hypercholesterolemia in Spain

Sánchez-Hernández, Rosa M.; Civeira, Fernando; Stef, Marianne; Pérez-Calahorra, Sofía; Almagro, Fátima; Plana, Núria; Nóvoa, Francisco J.; Sáenz-Aranzubía, Pedro; Mosquera, Daniel; Soler, Cristina; Fuentes, Francisco; Brito‐Casillas, Yeray; Real, José T.; Blanco‐Vaca, Francisco; Ascaso, Juan F.; Pocovı́, Miguel

doi:10.1161/circgenetics.116.001545

Cited by 60 publications

(27 citation statements)

References 44 publications

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“…However, since the presence of still undiagnosed HoFH cannot be excluded, the frequency could be even higher. This frequency is similar to that estimated in the Netherlands [35], whereas it is higher than the Spanish prevalence [37]. The screening of the APOB and PCSK9 genes in our population would have probably identified additional HoFH patients, further increasing the disease prevalence.…”

Section: Discussionsupporting

confidence: 87%

“…This difference becomes even more evident after therapy with statin, ezetimibe, and anti-PCSK9 antibodies. Similar data were also reported for a Spanish population of HoFH patients [37]. From this perspective, genetic screening could allow for a better characterization of the response to PCSK9 inhibitors in HoFH, although larger studies are required.…”

Section: Discussionsupporting

confidence: 80%

“…Whereas, among heterozygous FH patients, different phenotypes were observed on the basis of the variant type, being LDL-c in patients carrying a null variant higher than in patients carrying a defective variant [23,36]. However, no patients with two null variants were identified in this study, probably due to the fact that the severe phenotype in these patients are rarely observed [11,37].…”

Section: Discussioncontrasting

confidence: 54%

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A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia

Taranto

Giacobbe

Buonaiuto

et al. 2020

JCM

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Homozygous familial hypercholesterolemia (HoFH), the severest form of familial hypercholesterolemia (FH), is characterized by very high LDL-cholesterol levels and a high frequency of coronary heart disease. The disease is caused by the presence of either a pathogenic variant at homozygous status or of two pathogenic variants at compound heterozygous status in the LDLR, APOB, PCSK9 genes. We retrospectively analyzed data of 23 HoFH patients (four children and 19 adults) identified during the genetic screening of 724 FH patients. Genetic screening was performed by sequencing FH causative genes and identifying large rearrangements of LDLR. Among the HoFH patients, four out of 23 (17.4%) were true homozygotes, whereas 19 out of 23 (82.6%) were compound heterozygotes for variants in the LDLR gene. Basal LDL-cholesterol was 12.9 ± 2.9 mmol/L. LDL-cholesterol levels decreased to 7.2 ± 1.8 mmol/L when treated with statin/ezetimibe and to 5.1 ± 3.1 mmol/L with anti-PCSK9 antibodies. Homozygous patients showed higher basal LDL-cholesterol and a poorer response to therapy compared with compound heterozygotes. Since 19 unrelated patients were identified in the Campania region (6,000,000 inhabitants) in southern Italy, the regional prevalence of HoFH was estimated to be at least 1:320,000. In conclusion, our results revealed a worse phenotype for homozygotes compared with compound heterozygotes, thereby highlighting the role of genetic screening in differentiating one genetic status from the other.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 54%

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A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia

Taranto

Giacobbe

Buonaiuto

et al. 2020

JCM

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“… 1 A recent study in Spain has revealed a prevalence of one case in 450 000 individuals, which is higher than previously expected. 2 Lifelong exposure to elevated LDL-C values greatly increases the risk of atherosclerotic cardiovascular disease (ASCVD) and premature death; untreated HoFH patients often do not survive past the age of 30 years. 3 In order to reduce the risk of ASCVD in patients with HoFH, it is important to correctly diagnose patients as early as possible and provide aggressive interventions to reduce the cumulative LDL-C burden.…”

Section: Introductionmentioning

confidence: 99%

Management of homozygous familial hypercholesterolaemia in two brothers

et al. 2018

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Homozygous familial hypercholesterolaemia (HoFH) is a rare, genetic disorder of abnormally high levels of low-density lipoprotein cholesterol (LDL-C) requiring aggressive interventions to retard the evolution of atherosclerotic cardiovascular disease. We treated two brothers (ages 46 years and 47 years) with HoFH with statins, lipoproteinapheresis (LA) and the microsomal triglyceride transfer protein inhibitor lomitapide. Both brothers carried the p.Thr434Arg homozygous LDLR mutation and had childhood total cholesterol levels >700 mg/dL. Inter-LA LDL-C levels remained high; therefore, they were given escalating doses of oral lomitapide (5–10 mg/day). One brother was able to maintain LDL-C levels <70 mg/dL and stop LA. Lomitapide was well tolerated, with only an episode of headache requiring dose reduction from 40 mg/day to 20 mg/day in one patient. In two HoFH cases, lomitapide was an effective and well-tolerated adjunct therapy. Lomitapide doses required to maintain LDL-C goal levels appear to be lower in clinical practice than in clinical trials.

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“…Recent genetic studies of HoFH have highlighted the great variability of clinical phenotypes. 2 , 6 Indeed, HoFH is either caused by homozygosity or compound heterozygosity for mutations in the three major genes for LDL receptors, apolipoprotein B, and proprotein convertase subtilisin–kexin type 9 (PCSK9). The genetic heterogeneity in HoFH underlies the phenotypic variability.…”

Section: Discussionmentioning

confidence: 99%

A case report of an acute coronary syndrome in a 10-year-old boy with homozygous familial hypercholesterolaemia

Leclercq

Falcon‐Eicher

Farnier

et al. 2020

European Heart Journal - Case Reports

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Background Familial hypercholesterolaemia is a well-known disorder, but clinical diagnoses tend to be delayed. Acute coronary syndrome may occur in childhood. Case summary Our patient, a young boy with homozygous familial hypercholesterolaemia, complained of persistent chest pain at rest and suffered a non-ST-elevation myocardial infarction (NSTEMI). The diagnosis of NSTEMI was made on the basis of his clinical features, dynamic electrocardiogram changes, troponin elevation, and cardiac computed tomography findings. The patient was managed surgically by intrathoracic artery (ITA) bypass graft. During post-operative follow-up, the young patient suffered from angina pectoris from unexpected and exceptional atheroma stenosis on the ITA. Discussion Familial hypercholesterolaemia needs to be identified quickly in young patients and lipid lowering therapies should be started without delay.

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Homozygous Familial Hypercholesterolemia in Spain

Cited by 60 publications

References 44 publications

A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia

A Real-World Experience of Clinical, Biochemical and Genetic Assessment of Patients with Homozygous Familial Hypercholesterolemia

Management of homozygous familial hypercholesterolaemia in two brothers

A case report of an acute coronary syndrome in a 10-year-old boy with homozygous familial hypercholesterolaemia

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