Original Title: Pertinence de l’ajout du dépistage du rachitisme vitamino-dépendant au programme québécois de dépistage néonatal sanguin

Authors' objectives: In the Saguenay–Lac-Saint-Jean region, an increased prevalence of VDDR1A is attributed to a founder effect of the c.262delG variant in the CYP27B1 gene. Other variants have also been identified in the Quebec population but occur at much lower frequencies. Other forms of rickets are very rare or absent in the province of Quebec. The Ministry of Health and Social Services has mandated INESSS to evaluate the feasibility of implementing nationwide screening for vitamin D-dependent rickets in the Quebec Neonatal Blood Screening Program (PQDNS).

Authors' results and conclusions: RESULTS (#1 HEALTH PROBLEM ASSOCIATED WITH VITAMIN D-DEPENDENT RICKETS): Patients with vitamin D-dependent rickets may present with skeletal abnormalities, neurological and cardiac complications, dental defects, growth retardation, and developmental delays. (#2 VDDR1A): The CYP27B1 is responsible for converting 25(OH)D into its active form 1,25(OH)2D. • Symptoms typically appear between 2 and 24 months of age. (#3 HIGH PREVALENCE OF VDDR1A IS ASSOCIATED WITH A FOUNDER EFFECT IN SAGUENAY–LACSAINT-JEAN): • Among the Saguenay–Lac-Saint-Jean population, approximately 1 in 27 individuals is a carrier. The estimated birth prevalence ranges from 1 to 2,000 to 1 in 3,000, corresponding to roughly one affected birth per year to one every two years. • Quebec patients may have multiple genetic variants for the CYP27B1 gene (VDDR1A). (#4 PATIENTS WITH VDDR1A HAVE UNMET HEALTH NEEDS): • VDDR1A is not detectable at birth through standard biochemical or radiological testing. • Some patients may experience a period of diagnostic delay or uncertainty before receiving appropriate treatment. • Dental defects can have significant psychosocial impacts on patients. (#5 NEWBORN SCREENING FOR VITAMIN D-DEPENDENT RICKETS): • As part of a clinical study in Saguenay–Lac-Saint-Jean, a newborn screening test using buccal cells was developed specifically to detect the c.262delG variant in the CYP27B1 gene, with a very good performance in newborns. • Newborn screening for VDDR1A appears to be well accepted by parents who participated in the clinical study targeting the c.262delG variant. (#6 NEWBORN SCREENING FOR THE C.262DELG VARIANT IN THE CYP27B1 GENE (VDDR1A) WOULD INVOLVE SOME CHALLENGES): • Implementing newborn screening for VDDR1A within the PQDNS would require analytical verification of a test for the c.262delG variant. While the test was initially developed using buccal cell samples, the screening test for all eligible newborns relies on dried blood samples. • The scope of organizational changes required to introduce a new newborn screening test within the PQDNS will need to be carefully assessed.

Authors' recommendations: All scientific, contextual and experiential data collected - as well as the resulting findings - were presented and discussed with members of the Comité délibératif permanent – Approches diagnostiques et dépistage. The discussion focused exclusively on newborn screening for the c.262delG variant in the CYP27B1 gene associated with VDDR1A, as it is currently the only screening test available and the only variant with a prevalence of interest in Quebec. Following the completion of the evaluation and deliberation processes: INESSS does not recommend the addition of newborn screening for vitamin D-dependent rickets to the Quebec Neonatal Blood Screening Program. This position is largely based on the absence of evidence demonstrating that screening, as compared to clinical identification, leads to improved clinical outcome for affected children.

Authors' methods: A rapid review was conducted to document the clinical aspects, including test performance as well as the efficacy and safety of the newborn screening test. A narrative review of the scientific literature was performed to explore the population, sociocultural, organizational, - and economic dimensions. Relevant scientific and grey literature were identified across multiple databases without restrictions on study designs. Contextual and experiential data were gathered from an advisory committee of field professionals.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lajout-du-depistage-du-rachitisme-vitamino-dependant-au-programme-quebecois-de-depistage-neonatal-sanguin.html

Year Published: 2025

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/pertinence-de-lajout-du-depistage-du-rachitisme-vitamino-dependant-au-programme-quebecois-de-depistage-neonatal-sanguin.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)