title: Premature atherosclerosis is not systematic in phytosterolemic patients: severe hypercholesterolemia as a confounding factor in five subjects.
abstract: OBJECTIVE
  Phytosterolemia is a rare autosomal recessive disorder characterized by dramatically elevated circulating levels of plant sterols (PS). Phytosterolemia is believed to be responsible for severe premature atherosclerosis. The clinical, biological and molecular genetic features of 5 patients with phytosterolemia and transient severe hypercholesterolemia challenge this hypothesis.
  
  
  METHODS
  Our patients were referred for suspected homozygous familial hypercholesterolemia. Despite the phenotype, this diagnosis was invalidated and phytosterolemia was confirmed by the identification of mutations in the ABCG5/ABCG8 transporter complex. Plasma PS were analyzed with a mass spectrometric-gas chromatographic procedure. Vascular status was assessed with carotid ultrasonography and completed (for 4 of the 5 patients) with femoral ultrasonography; additional examinations of cardiovascular status included a stress test, determination of coronary calcium score, echocardiography, non-invasive assessment of endothelium-dependent dilatation and coronarography.
  
  
  RESULTS
  The 5 patients displayed markedly elevated levels of both β-sitosterol and campesterol (15-30 fold higher than normal values). However, none displayed significant signs of infraclinical premature atherosclerosis (respectively at the ages of 32, 27, 29, 11 and 11 years). All patients were characterized by very high levels of total (>450 mg/dl) and LDL-cholesterol (>350 mg/dl) at diagnosis which decreased markedly on dietary intervention alone. Treatment with cholestyramine or Ezetimibe ± atorvastatin normalized cholesterol levels, although plasma PS concentrations remained elevated.
  
  
  CONCLUSIONS
  The clinical and biological characteristics of our patients, considered together with reports of cases which equally lack CVD, support the contention that the premature atherosclerosis associated with phytosterolemia in some patients may be due at least in part to mechanisms independent of elevated circulating phytosterol levels.
authors.affiliation: Département d'Endocrinologie, Diabétologie et Nutrition, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; Institute of Cardiometabolism and Nutrition, Paris, France; Université Paris-Diderot, Paris 7, Paris, France. Electronic address: boris.hansel@gmail.com.
authors.forename: Boris
authors.initials: B
authors.lastname: Hansel
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France; Service de Biochimie endocrinienne et oncologique, Centre de Génétique Moléculaire et Chromosomique, AP-HP, Hôpital de la Pitié, Paris, France; Dyslipidemia and Atherosclerosis Research Unit, INSERM-UMRS 939, Hôpital de la Pitie, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Carrié
authors.affiliation: Unité de Néphrologie-Métabolisme pédiatrique, Département de Pédiatrie, Hôpitaux Universitaires de Genève, Genève, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brun-Druc
authors.affiliation: Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Leclert
authors.affiliation: Laboratoire CRRET, EAC/CNRS-7149, Université Paris Est Créteil, Faculté des Sciences et Technologie, 61 av du Général de Gaulle, 94010 Créteil, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chantepie
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France; Service de Biochimie endocrinienne et oncologique, Centre de Génétique Moléculaire et Chromosomique, AP-HP, Hôpital de la Pitié, Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Coiffard
authors.affiliation: Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Kahn
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France; Dyslipidemia and Atherosclerosis Research Unit, INSERM-UMRS 939, Hôpital de la Pitie, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France; Dyslipidemia and Atherosclerosis Research Unit, INSERM-UMRS 939, Hôpital de la Pitie, Paris, France; Service d'Endocrinologie-Métabolisme, AP-HP, Hôpital de la Pitié, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D050197:Atherosclerosis / Q000209:etiology*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D007410:Intestinal Diseases / Q000150:complications*; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications*; D010840:Phytosterols / Q000009:adverse effects*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D010840:Phytosterols
keywords: Cardiovascular disease; Hypercholesterolemia; Phytosterolemia; Plant sterols; Premature atherosclerosis; Sitosterolemia