title: Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives.
abstract: Familial hypercholesterolemia (FH) is a co-dominantly inherited disorder of plasma lipoprotein metabolism. The prevalence of heterozygous FH (HeFH) is between 1/500 and 1/200 whereas that of homozygous form (HoFH) is about 1/1,000,000. Diagnosis is based on cutaneous xanthomas and untreated levels of LDL-cholesterol over 500 mg/dl before 10 years of age. Life expectancy, without treatment, does not exceed 20 years of age. The aim of this study is to characterise in details a cohort of 8 HoFH paediatric patients in order to illustrate all the current therapeutic options and to add some clinical and genetic information about this rare disease. We collected demographic, clinical, biological, imaging and genotype details. Furthermore, clinical and biochemical response to different treatment methods was retrospectively evaluated. All patients had genetically proven HoFH. All patients were subject to a lipid-lowering diet and medical treatment (except one), three patients underwent a liver transplant and one an hepatocytes infusion. Medical treatment was well tolerated with a median reduction of 44% and 47% in LDL-Cholesterol and Total Cholesterol respectively. The hepatocytes transplant produced a further, though slight, decrease in cholesterol levels as opposed to medical therapy alone. Transplanted patients normalized their cholesterol levels. Since the very high cardiovascular risk, HoFH requires immediate diagnosis, treatment and monitoring. Nowadays, the use of statins remains the cornerstone of medical therapy and liver transplantation is the possibly curative therapy. Besides, high hopes are pinned in new drugs (antibody targeting PCSK9, Mipomersen and Lomitapide) and stem cells.
authors.affiliation: Université catholique de Louvain, Cliniques Universitaires Saint Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgium.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sanna
authors.affiliation: Université catholique de Louvain, Cliniques Universitaires Saint Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Stéphenne
authors.affiliation: Université catholique de Louvain, Cliniques Universitaires Saint Luc, Centre de Génétique Humaine, Bruxelles, Belgium.
authors.forename: Nicole
authors.initials: N
authors.lastname: Revencu
authors.affiliation: Université catholique de Louvain, Cliniques Universitaires Saint Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Smets
authors.affiliation: UF Lipides-Dyslipidémies, Laboratoire de Biochimie, CBE, 59 boulevard Pinel, Bron Cedex, France; INSERM U1060, INSA de Lyon, INRA U1235, Univ Lyon-1, Université de Lyon, Villeurbanne, Oullins, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Sassolas
authors.affiliation: UF Lipides-Dyslipidémies, Laboratoire de Biochimie, CBE, 59 boulevard Pinel, Bron Cedex, France; INSERM U1060, INSA de Lyon, INRA U1235, Univ Lyon-1, Université de Lyon, Villeurbanne, Oullins, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Di Filippo
authors.affiliation: Centre Hospitalier Regional de Jolimont, Haine-Saint-Paul, Belgium.
authors.forename: Olivier S
authors.initials: OS
authors.lastname: Descamps
authors.affiliation: Université catholique de Louvain, Cliniques Universitaires Saint Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgium. Electronic address: etienne.sokal@uclouvain.be.
authors.forename: Etienne M
authors.initials: EM
authors.lastname: Sokal
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood*; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D018752:Diet, Fat-Restricted; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D022781:Hepatocytes / Q000637:transplantation; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011973:Receptors, LDL / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D005819:Genetic Markers; C573412:LDLR protein, human; D011973:Receptors, LDL; D002784:Cholesterol
keywords: Familial hypercholesterolemia; Hepatocyte transplantation; LDL-receptor mutations; Liver transplantation; Proprotein convertase subtilisin-like kexin type 9; Statins