We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genotype-phenotype Description of Vitamin D--dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.
- Authors
Méaux, Marie-Noëlle; Harambat, Jérôme; Rothenbuhler, Anya; Léger, Juliane; Kamenicky, Peter; Soskin, Sylvie; Boyer, Olivia; Boros, Emese; D'Anella, Pascal; Mignot, Brigitte; Gebhart, Maite; Vic, Philippe; Richard, Nicolas; Thivichon-Prince, Béatrice; Francou, Bruno; Linglart, Agnès; Bacchetta, Justine; Molin, Arnaud
- Abstract
Introduction: Vitamin D--dependent rickets type 1A (VDDR1A) is a rare genetic disease associated with loss-of-function variations in the gene encoding the vitamin D--activating enzyme 1α-hydroxylase (CYP27B1). Phenotype-genotype correlation is unclear. Long-term outcome data are lacking. The objective of this study was to describe characteristics and outcomes to search for a phenotype-genotype correlation. Methods: We retrospectively collected clinical data, genetic features, and outcomes from 24 genetically confirmed cases from 10 French centers; results are presented as median (min--max). Results: Clinical symptoms at diagnosis (age, 1.5 [0.5-8.7] years) were mainly bone and neurological abnormalities, and laboratory data showed hypocalcemia (1.97 [1.40-2.40] mmol/L), hypophosphatemia (-3.4 [-13.4 to (-)0.2] SD score for age), low 25OHD and low 1,25(OH)2D3, secondary hyperparathyroidism with PTH at 6.6 (1.3-13.7) times the upper limit for normal (ULN; PTH expressed as ULN to homogenize data presentation), and increased alkaline phosphatase (1968 [521-7000] IU/L). Bone radiographs were abnormal in 83% of patients. We identified 17 variations (11 missense, 3 frameshift, 2 truncating, and 1 acceptor splice site variations) in 19 families (homozygous state in 58% [11/19]). The partial loss-of-function variation p.(Ala129Thr) was associated with a milder phenotype: older age at diagnosis, higher serum calcium (2.26 vs 1.85 mmol/L), lower PTH (4.7 vs 7.5 ULN), and lower alkaline phosphatase (759 vs 2082 IU/L). Patients were treated with alfacalcidol. Clinical (skeletal, neurological), biochemical, and radiological outcomes were satisfactory, and complications occurred if there was bad adherence. Conclusion: Overall, our findings highlight good outcomes under substitutive treatment and the need of a closer follow-up of eyes, teeth, kidneys, and blood pressure in VDDR1A.
- Subjects
RICKETS treatment; GENETIC disorders; HYDROXYLASES
- Publication
Journal of Clinical Endocrinology & Metabolism, 2023, Vol 108, Issue 4, p812
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgac639