Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives

Sanna, Claudia; Stéphenne, Xavier; Revençu, Nicole; Smets, Françoise; Sassolas, Agnès; Filippo, Mathilde Di; Descamps, Olivier; Sokal, Étienne

doi:10.1016/j.atherosclerosis.2016.02.009

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…Treatment options include dietary modifications, life style changing, medical treatment, lipid or LDL aphaeresis, and LT. Cornerstone of the medical therapy is the use of statin, which can be combined with ezetimibe and/or cholestyramine . However, all published data have shown that these treatments achieve just a delay of disease progression rather than being an effective treatment, especially for the homozygous type of FH .…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment

Alim

Tokat

Erdoğan

et al. 2016

Pediatric Transplantation

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FH is an autosomal dominant genetic disorder characterized by increased TC and LDL level, which leads to xanthomas, atherosclerosis, and cardiac complications even in childhood. The treatment options are diet, medical treatment, lipid apheresis, and LT. The aim of our study was to analyze our data of patients with FH. Between 2004 and 2015, there were 51 patients who underwent pediatric LT at our center. All patients with FH were identified, and the data were retrospectively analyzed. There were eight patients with homozygous FH in the median age of 10 years (IQR 6-12) who underwent LT. The median pre-operative TC and LDL levels were 611 mg/dL (IQR: 460-844) and 574 mg/dL (IQR: 398-728) and decreased to normal levels 1 week after LT (TC: 193 mg/dL and LDL: 141 mg/dL). Two patients died two and 18 months after LT due to sudden cardiac arrest. Both patients were diagnosed with cardiovascular disease pre-operatively. The LT is the only curative treatment for this disease. To achieve an excellent outcome, it should be performed before the development of cardiovascular disease, because the regression of severe cardiovascular disease after transplantation is limited.

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Section: Discussionmentioning

confidence: 99%

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment

Alim

Tokat

Erdoğan

et al. 2016

Pediatric Transplantation

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“…All the patients meet the FH Dutch diagnostic criteria for definite FH, except patient 3 and 4, who had a possible and probable FH, respectively, both detected by universal FH screening ( Klancar et al, 2015 ; Groselj et al, 2018 ); all patients were genetically diagnosed for FH. Four patients presented xanthomas, whereas in France ( Bruckert et al, 2017 ), Austria ( Widhalm et al, 2017 ), and Belgium ( Sanna et al, 2016 ) almost all of the patients had skin stigmata at the diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…If LDL-apheresis is not successful, liver transplantation can be an alternative, considering also as a successful therapy in other metabolic liver diseases ( McKiernan, 2017 ). In the Brussels cohort published by Sanna, the median reduction in TC in response to pharmacological treatment was 47% ( Sanna et al, 2016 ). In our cohort, we observed a median decrease of TC levels in response to the combined treatment by 28% (range from a reduction of 69% to an increase of 15% besides the therapy).…”

Section: Discussionmentioning

confidence: 99%

Genetic and Clinical Characteristics of Patients With Homozygous and Compound Heterozygous Familial Hypercholesterolemia From Three Different Populations: Case Series

et al. 2020

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Homozygous familial hypercholesterolemia (HoFH) and compound heterozygous familial hypercholesterolemia (cHeFH) are rare disorders generated by disease-causing variants in both alleles of the LDLR or other familial hypercholesterolemia (FH)-related genes. HoFH and cHeFH are characterized by severely elevated low-density lipoprotein-cholesterol (LDL-C), frequently leading to early cardiovascular disease. We investigated the genetic and clinical characteristics of HoFH and cHeFH patients from the Slovenian FH registry and/or those who were previously diagnosed or managed at our institution (Slovenian, Pakhtun and Albanian ethnicity), where genetic testing is not available. Our study includes seven patients. Their median age at the time of clinical diagnosis was 6.3 years (2.9–12.9 years); 2/7 were females. Two patients were diagnosed through the universal FH screening and five patients were diagnosed due to the presence of xanthomas. All the mutations are present in LDLR gene: 7 different genotypes for HoFH (p.Cys167Leu, p.Asp178Asn, p.Cys243Tyr, p.Gly549Asp, p.Cys27Trp, p.Ile585Thr and p.Val797Met) and p.Gly549Asp/p.Gln384Pro genotype for cHeFH patient. The median initial level of LDL-C was 17.0 mmol/L [655 mg/dL] (range 7.6–21.6 mmol/L). The HoFH/cHeFH patients are clinically and genetically very diverse. The clinical criteria (as Simon Broome criteria) might be applicable already in children to raise suspicion of FH but in some cases fail to distinguish heterozygous FH and HoFH/cHeFH patients. However, genetic testing is helpful in confirming the diagnosis, also for a prompt awareness, better compliance to treatment and family screening.

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“…Another similar study showed normalization of LDL levels within 1 week after the operation (Alim et al, 2016 ). However, it must be noted that in order to be curative, the procedure should be performed before CVD is established (Alim et al, 2016 ; Sanna et al, 2016 ). Indeed, given the lack of CHD outcome data, more such studies are needed to evaluate the long-term efficacy of this approach (Martinez et al, 2016 ).…”

Section: Management Of Fhmentioning

confidence: 99%

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

et al. 2018

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Familial hypercholesterolemia (FH) is a common genetic cause of premature cardiovascular disease (CVD). The reported prevalence rates for both heterozygous FH (HeFH) and homozygous FH (HoFH) vary significantly, and this can be attributed, at least in part, to the variable diagnostic criteria used across different populations. Due to lack of consistent data, new global registries and unified guidelines are being formed, which are expected to advance current knowledge and improve the care of FH patients. This review presents a comprehensive overview of the pathophysiology, epidemiology, manifestations, and pharmacological treatment of FH, whilst summarizing the up-to-date relevant recommendations and guidelines. Ongoing research in FH seems promising and novel therapies are expected to be introduced in clinical practice in order to compliment or even substitute current treatment options, aiming for better lipid-lowering effects, fewer side effects, and improved clinical outcomes.

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Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives

Cited by 18 publications

References 38 publications

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment

Genetic and Clinical Characteristics of Patients With Homozygous and Compound Heterozygous Familial Hypercholesterolemia From Three Different Populations: Case Series

Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management

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