{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:01:50Z","timestamp":1791489710824,"version":"4.3.4"},"reference-count":37,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Vitamin D\u2013dependent rickets type 1A (VDDR1A) is a rare genetic disease associated with loss-of-function variations in the gene encoding the vitamin D\u2013activating enzyme 1\u03b1-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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively collected clinical data, genetic features, and outcomes from 24 genetically confirmed cases from 10 French centers; results are presented as median (min\u2013max).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (\u22123.4 [\u221213.4 to (\u2212)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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgac639","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T09:52:46Z","timestamp":1667382766000},"page":"812-826","source":"Crossref","is-referenced-by-count":9,"title":["Genotype-phenotype Description of Vitamin D\u2013dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-1926","authenticated-orcid":false,"given":"Marie-No\u00eblle","family":"M\u00e9aux","sequence":"first","affiliation":[{"name":"CHU de 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