ESPN 54th Annual Meeting

ESPN 2022


 
VITAMIN-D DEPENDENT RICKETS TYPE 1A: PHENOTYPE GENOTYPE CHARACTERIZATION OF 24 PATIENTS WITH CYP27B1 MUTATION
MEAUX MARIE-NOëLLE 12 HARAMBAT JéROME 3 ROTHENBUHLER ANYA 4 LéGER JULIANE 4 KAMENICKY PETER 4 SYLVIE SOSKIN 5 BOYER OLIVIA 4 EMESE BOROS 6 DANELLA PASCAL 7 MIGNOT BRIGITTE 8 GEBHART MAITE 8 VIC PHILIPPE 9 RICHARD NICOLAS 10 THIVICHON-PRINCE BEATRICE 11 FRANCOU BRUNO 4 LINGLART AGNES 4 BACCHETTA JUSTINE 11 MOLIN ARNAUD 2

1- CHU DE LYON, SERVICE DE NéPHROLOGIE, RHUMATOLOGIE ET DERMATOLOGIE PéDIATRIQUES, LYON, FRANCE
2- CHU DE CAEN, SERVICE DE GéNéTIQUE, CAEN, FRANCE
3- BORDEAUX
4- PARIS
5- STRASBOURG
6- BRUXELLES
7- AVIGNON
8- BESANÇON
9- QUIMPER
10- CAEN
11- LYON
12- CHU de Bordeaux, Service de Néphrologie Pédiatrique, Bordeaux, France
 
Introduction:

Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disease due to biallelic loss of function variants in the CYP27B1 gene, encoding the 1α-hydroxylase enzyme that activates vitamin D. The objectives of this study were to describe clinical data, genetic features and outcomes in a European population of VDDR1A, and to analyze genotype – phenotype correlations.

Material and methods:

We performed a multicentric retrospective study. Data from 24 genetically confirmed cases of VDDR1A from 10 centers were retrospectively reviewed. Data are presented as median [min - max].

Results:

Clinical symptoms at diagnosis were mainly bone and neurological abnormalities. Age at diagnosis was 1.5 [0.5 - 8.7] years. Laboratory data at diagnosis showed mild hypocalcemia (1.97 [1.40 - 2.40] mmol/L) and hypophosphatemia (- 3.4 [- 13.4 - (-) 0.2] SDS), low 25OHD (23 [7 - 81] ng/mL) and low 1,25(OH)2D3 (14 [7 - 82] pg/mL), secondary hyperparathyroidism with PTH at 6.6 [1.3 - 13.7] times ULN and increased alkaline phosphatases (2041 [521 - 7000] UI/L). Bone X-rays were abnormal for 80% patients. Outcome under substitutive treatment by alfacalcidol (median dose 1 µg/day) was considered satisfactory in case of good adherence. Median adult height was 164 centimeters (160 in women, 167 in men). Median blood pressure at last follow-up was at the upper limit normal. Five cases of nephrocalcinosis were described, which normalized. Dental abnormalities were frequent. There were 17 different mutations and the recurrent p.(Ala129Thr) substitution (1 compound heterozygous and 4 homozygous cases) was associated with a milder phenotype with older age at diagnosis and often normocalcemia.

Conclusions:

VDDR1A is a rare, genetically heterogenous disease. Our findings are consistent with previous studies except for younger age at diagnosis, inconstant hypocalcemia and lower 25OHD levels. They highlight the need of closer follow-up of eyes, teeth, kidneys and blood pressure in these patients.