Novel Vitamin D Resistant Type II Rickets in the Domestic Cat

Bone anomalies are caused by a lack of calcium uptake due to vitamin D deficiency, which can be caused by genetic defects or environmental factors, such as malnutrition. Rickets is characterized by softening of the bones (osteomalacia), resulting in increased incidences of fractures and deformity. Vitamin D plays a key role in dietary calcium absorption and genetic variation within gene(s) interacting with Vitamin D are often associated with the disorder. A juvenile cat presented with normal 25-hydroxyvitamin D levels, and dietary deficiencies were excluded. Calcitriol, normally used to treat low calcium levels, was initially tested in the patient, and a 89 pmol/L concentration was detected, far below the median of 221 pmol/L. To date, three genetic variants in CYP27B1 in cats are associated with vitamin D resistant rickets. The patient tested wild-type for all the know variants. Using the 99Lives database of 73 whole genome sequenced cats, 20 variants in CYP27B1 and 44 variants in VDR were identified. To exclude a novel variant within the CYP27B1 and VDR genes, the entire CDS of both genes was sequenced in the affected cat. No novel variants were identified in CYP27B1, and three non-synonymous variants were found in VDR. The identified variants in VDR are being genotyped in a wider population to support causality.