Genotype-phenotype Description of Vitamin D–dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease
Authors' 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.
Study context
- Population
- Genetically confirmed vitamin D-dependent rickets type 1A (VDDR1A; CYP27B1 loss-of-function variants), 10 French centers19 families
- Participants
- 24 participants
- Exposure
- CYP27B1 p. variant vs other variants
- Outcome
- Characteristics at diagnosis
- Follow-up
- Diagnosis
Methodological detailsmulticentre (10 French centers), genotype-phenotype correlation
- Multicentre (10 French centers)
- Genotype-phenotype correlation
Main finding
As reported in the abstract
- Age at diagnosis, median (min-max)
- 1.5 (0.5-8.7) years
- Serum calcium, median (min-max)
- 1.97 (1.40-2.40) mmol/L
- Phosphate, median (min-max)
- −3.4 (−13.4 to (-)0.2) SD score for age
- PTH, median (min-max)
- 6.6 (1.3-13.7) times upper limit for normal (ULN)
- Alkaline phosphatase, median (min-max)
- 1968 (521-7000) IU/L
- Abnormal bone radiographs
- 83%
Observational data: associations, not effects.
Further findings
Genetics
- Variations identified (11 missense, 3 frameshift, 2 truncating, 1 acceptor splice site)
- 17
- Homozygous state
- 58% (11/19)
Genotype-phenotype: p.(Ala129Thr) partial loss-of-function variant
- P.(Ala129Thr) associated with milder phenotype: older age at diagnosis, higher serum calcium, lower PTH, lower alkaline phosphatase
Outcomes under alfacalcidol
- Clinical (skeletal, neurological), biochemical and radiological outcomes satisfactory
Safety
- Complications occurred with bad adherence
Original publication
Genotype-phenotype Description of Vitamin D–dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease. J Clin Endocrinol Metab. Published 2 November 2022. doi:10.
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