Vitamin D-Dependent Rickets Type 1A in Two Siblings with a Hypomorphic CYP27B1 Variant Frequent in the African Population.

ABSTRACT

Vitamin D-dependent type 1A rickets (VDDR-1A) is a rare autosomal recessive disease due to the inability to convert 25-hydroxyvitamin D [25(OH)D] to the active form 1.25-dihydroxyvitamin D [1.25(OH) 2 D] by the enzyme 25(OH)D-1α-hydroxylase leading to low or low-normal serum levels of [1.25(OH) 2 D]. We report two sisters with rickets in whom the diagnosis of VDDR-1A was a challenge. They had normal 1.25(OH)2D levels, which are unusual with this condition but may be explained by the identified genotype. Both have compound heterozygous for two, most likely, hypomorphic CYP27B1 alleles the novel p.(Arg117Gly) variant, and p.(Ala129Thr), which are present in 0.43% of the African population. This report illustrates the variability of clinical, laboratory, and radiological presentation between two sisters with the same genotype, during phases of faster or slower growth. Genetic testing was crucial for establishing the diagnosis that optimized the management and genetic counseling.