title: Establishment of reference values of α-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia.
abstract: Chylomicron retention disease (CMRD), a rare genetic hypocholesterolemia, results in neuro-ophtalmologic damages, which can be prevented by high doses of vitamin E during infancy. In these patients, plasma vitamin E concentration is significantly reduced due to defects of chylomicron secretion. Vitamin E in adipose tissue (AT) and red blood cells (RBC) have been proposed as potential relevant biomarkers of vitamin E status but no reference values in children are available. The objectives were (i) to establish age-reference intervals in healthy children for α-tocopherol in plasma, red blood cells (RBC) and adipose tissue (AT) and (ii) to determine the variations of α-tocopherol in patients with CMRD after oral treatment with vitamin E.
  
  
  
  This prospective study included 166 healthy children (1 month - 18 years) and 4 patients with CMRD. Blood and AT were collected in healthy children during a scheduled surgery and in patients before and after a 4-month treatment with α-tocopherol acetate.
  
  
  
  The reference ranges for α-tocopherol were 11.9 - 30 μmol/L in plasma, 2.0 - 7.8 μmol/L packed cells in RBC and 60 - 573 nmol/g in AT. α-tocopherol levels in plasma correlated with those of RBC (r = 0.31; p < 0.01). In patients with CMRD after 4 months treatment, α-tocopherol concentrations remained less than 70 % of the control values in plasma, increased by 180 % to reach normal values in RBC, and remained stable in the normal range in AT.
  
  
  
  This study establishes pediatric reference intervals for α-tocopherol in plasma, RBC and AT. These values will be beneficial in assessing accurate α-tocopherol status in children and to optimize the monitoring of rare diseases such as CMRD. Our data suggest that RBC α-tocopherol, appears as a relevant biomarker to appreciate the effectiveness of treatment with α-tocopherol in patients with a rare primary hypocholesterolemia. The biopsy of AT could be used at diagnosis to assess the severity of the vitamin E deficiency and periodically after a long duration of vitamin E therapy to assess whether the treatment is effective, based on reference intervals defined in this study.
authors: Biochemistry Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France.|INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.
authors: Charlotte
authors: C
authors: Cuerq
authors: Pediatric Hepato-Gastroenterology and Nutrition Unit, Hôpital Femme Mère Enfant de Lyon, Hospices Civils de Lyon, Lyon, Bron, France.
authors: Lioara
authors: L
authors: Restier
authors: Biochemistry Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France.|INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.
authors: Jocelyne
authors: J
authors: Drai
authors: Biochemistry Department, Lyon Sud Hospital, Hospices Civils de Lyon, Lyon, France.|INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.
authors: Emilie
authors: E
authors: Blond
authors: Hospices Civils de Lyon, Pole IMER, Lyon, France.
authors: Adeline
authors: A
authors: Roux
authors: INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.|Fédération d'endocrinologie, maladies métaboliques, diabète et nutrition, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, Bron, France.
authors: Sybil
authors: S
authors: Charriere
authors: INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.
authors: Marie-Caroline
authors: MC
authors: Michalski
authors: INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.|Dyslipidemia Unity, Department of Biochemistry and Molecular Biology, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Lyon, Bron, France.
authors: Mathilde
authors: M
authors: Di Filippo
authors: Research Centre, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, H3T 1C5, Canada.|Department of Nutrition, Université de Montréal, Montréal, Québec, H3T 1A8, Canada.
authors: Emile
authors: E
authors: Levy
authors: INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France.|Pediatric Hepato-Gastroenterology and Nutrition Unit, Hôpital Femme Mère Enfant de Lyon, Hospices Civils de Lyon, Lyon, Bron, France.
authors: Alain
authors: A
authors: Lachaux
authors: INSERM U1060, INRA UMR 1397, INSA-Lyon, CarMeN Laboratory, Université Lyon 1, Lyon, France. noel.peretti@chu-lyon.fr.|Pediatric Hepato-Gastroenterology and Nutrition Unit, Hôpital Femme Mère Enfant de Lyon, Hospices Civils de Lyon, Lyon, Bron, France. noel.peretti@chu-lyon.fr.
authors: Noël
authors: N
authors: Peretti
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood* / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D008286:Malabsorption Syndromes / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000378:metabolism; D011446:Prospective Studies; D012016:Reference Values; D014810:Vitamin E / Q000097:blood / Q000378:metabolism; D024502:alpha-Tocopherol / Q000097:blood* / Q000378:metabolism*
chemical_list: D014810:Vitamin E; D024502:alpha-Tocopherol
keywords: Adipose tissue; Anderson’s disease; Chylomicron retention disease; Primary hypocholesterolemia; Red blood cells; Reference interval; Vitamin E; α-tocopherol