Hypercalcemie par mutation inactivatrice du CYP24A1. Etude d'un cas et revue de la litterature.

CYP24A1; Hypercalcemia; Hypercalcemie; Lithiase; Lithiasis; Ratio 25 hydroxyvitamine D/24,25 hydroxyvitamine D; Ratio 25-hydroxyvitamin D/24,25-hydroxyvitamin D

Abstract :

[en] We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%. The loss of peripheral catabolism of vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is responsible for persistent high levels of 1,25-dihydroxyvitamin D especially after sun exposure and a charge of native vitamin D. Although there are currently no recommendations (French review) on this subject, this disease should be suspected in association with recurrent calcium stones with nephrocalcinosis, and a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone levels. Resistance to corticosteroid therapy distinguishes it from other calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25 hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24-hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step. The current therapeutic management includes the restriction native vitamin D supplementation and the limitation of sun exposure. Biological monitoring will be based on serum calcium control and modulation of parathyroid hormone concentrations.

Disciplines :

Urology & nephrology
Laboratory medicine & medical technology

Author, co-author :

Seidowsky, Alexandre

Villain, Cedric

Vilaine, Eve

Baudoin, Roselyne

Tabarin, Antoine

Kottler, Marie-Laure

Cavalier, Etienne ; Université de Liège > Département de pharmacie > Chimie médicale

Souberbielle, Jean-Claude

Massy, Ziad A.

Language :

French

Title :

Hypercalcemie par mutation inactivatrice du CYP24A1. Etude d'un cas et revue de la litterature.

Alternative titles :

[en] Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature review

Publication date :

April 2017

Journal title :

Néphrologie et Thérapeutique

ISSN :

1769-7255

eISSN :

1872-9177

Publisher :

Elsevier Masson, Netherlands

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 04 July 2017

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