Vitamin D-deficiency rickets, type II

Gene: VDR

Transmission: Autosomal, likely recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Deletion, VDR gene; c.106 del.C, p.(Arg36Glu frameshift STOP 18), exon2, chr.B4.

Breed: Domestic longhair

Medical system: Skeletal

Age of onset of symptoms: From 3 months.

Rickets is a medical condition involving weak, soft bones due to inadequate calcification of bone tissue.  Additional symptoms include bone pain, bone deformities and bone fractures.  Rickets is caused by a deficiency in functional calciferol (vitamin D) because of an inadequate diet or because of a genetic lesion.  Vitamin D is needed for adequate intestinal absorption of calcium and phosphate, as required for proper bone mineralization.  Genetic causes of rickets are named Vitamin D-dependent rickets (VDDR) and are classified as VDDR1A, caused by mutations in the kidney enzyme CYP27B1; VDDR1B, caused by mutations in the liver enzyme CYP2R1; and VDDR2A, caused by mutations in VDR, the calcitriol (vitamin D) receptor.

A 14-week-old domestic kitten was presented with lameness and failure to grow despite a good appetite.  X-ray images were consistent with a diagnosis of rickets.  DNA studies identified a homozygous inactivating mutation within the calciferol (vitamin D) receptor, confirming the diagnosis of VDDR2A.  A healthy sibling tested negative for the mutation, as did 400 additional cats tested.  The frequency of the causative mutation within the domestic cat population remains to be determined.

Vitamin D-deficiency rickets (VDDR) in the cat is sporadically reported due to additional mutations in calciferol production or function:

VDDR type IA – CYP27B1 gene, OMIA link: [0837-9685]

VDDR type IB – CYP2R1 gene, OMIA link: [2221-9685]

References:

OMIA link: [1431-9685]

Habacher G, Malik R, Lait PJ, et al. (2023) Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2. J Feline Med Surg 25:1098612X231165630. [pm/37387221]

Clarke KE, Hurst EA, Mellanby RJ, (2021) Vitamin D metabolism and disorders in dogs and cats. J Small Anim Pract 62:935-947.  [pm/34323302]

Contributed by: Kayla Cyr and Alexanne Guy, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)