ENPP1 and osteoporosis: The Y471C and H777C variant alleles were found to reduce ENPP1 enzymatic velocity by 70% and 95% compared with the WT enzyme, respectively, suggesting that ENPP1 deficiency may induce gene-dose effects, such that the variable degrees of ENPP1 pathogenic variants can modify the phenotype: Phosphate wasting occurred in both biallelic and monoallelic deficient family members, but monoallelic members exhibited osteoporosis in middle age rather than rickets in infancy and adolescence.