Establishment of reference values of alpha-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia

C. Cuerq , L. Restier , Jocelyne Drai (1, 2) , Emilie Blond (2) , A. Roux , S. Charriere , Marie-Caroline Michalski , Mathilde Di Filippo (2) , E. Levy , A. Lachaux , N. Peretti

1 Départment de Biochimie
2 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

BACKGROUND: 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 alpha-tocopherol in plasma, red blood cells (RBC) and adipose tissue (AT) and (ii) to determine the variations of alpha-tocopherol in patients with CMRD after oral treatment with vitamin E. METHODS: 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 alpha-tocopherol acetate. RESULTS: The reference ranges for alpha-tocopherol were 11.9 - 30 mumol/L in plasma, 2.0 - 7.8 mumol/L packed cells in RBC and 60 - 573 nmol/g in AT. alpha-tocopherol levels in plasma correlated with those of RBC (r = 0.31; p \textless 0.01). In patients with CMRD after 4 months treatment, alpha-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. CONCLUSION: This study establishes pediatric reference intervals for alpha-tocopherol in plasma, RBC and AT. These values will be beneficial in assessing accurate alpha-tocopherol status in children and to optimize the monitoring of rare diseases such as CMRD. Our data suggest that RBC alpha-tocopherol, appears as a relevant biomarker to appreciate the effectiveness of treatment with alpha-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.

Mots clés: alpha-tocopherol; red blood cells; adipose tissue; primary hypocholesterolemia; anderson's disease; chylomicron retention disease; reference interval

Mots clés: vitamin E

Domaines: Sciences du Vivant [q-bio]

C. Cuerq, L. Restier, Jocelyne Drai, Emilie Blond, A. Roux, et al.. Establishment of reference values of alpha-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia. Orphanet Journal of Rare Diseases, 2016, 11 (1), pp.114. ⟨10.1186/s13023-016-0498-8⟩. ⟨hal-01850299⟩