Vitamin D is a key factor to mineral homeostasis and bone mineralization, which explains growth plate lesions and long bone deformities described in nutritional vitamin D deficiency associated rickets. Vitamin D requires a two-step enzymatic activation process (namely 25- and 1α-hydroxylation) to form calcitriol which activates its receptor and exerts its physiological functions. Among the group of genetically determined rare diseases called vitamin D resistant rickets, loss-of-functions variants in genes encoding vitamin D activation enzymes (CYP2R1, CYP27B1) and receptor (VDR) have been associated with autosomal recessive diseases resulting from a defective vitamin D activation or activity unable to sustain the growing skeleton mineral needs, with some degree of phenotype-genotype correlation. More recently, pangenomic analyzes such as whole exome sequencing have been used to pinpoint a neomorphic variant in CYP3A3, encoding a liver xenobiotic metabolizing enzyme, in an autosomal dominant form of rickets resulting from an enhanced and deregulated vitamin D degradation. A precise etiologic diagnosis in genetic rickets, based on biochemical characterization (including vitamin D metabolites above mineral metabolism biomarkers) and genetic analysis, is of utmost importance as it allows adapted genetic counselling and relative screening, and the use of the proper therapy, in a context where new drugs are now available or being developed in other forms of genetic rickets and bone metabolic diseases. The objective of this talk will be to review variants previously identified within the above-mentioned genes and to discuss how this knowledge would help in the context of growing use of pangenomic clinical testing (whole exome or whole genome sequencing) for patients but also for genomic newborn screening. For illustration, we will use data and examples from a single reference genetic diagnosis laboratory in France and French national whole genome sequencing laboratories (SeqOIA and AURAgen).