Vitamin D-deficiency, type 1B (CYP2R1-linked)

Gene: CYP2R1

Transmission: Autosomal recessive (most likely)

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, CYP2R1 gene: c.1386 del.T; p.(F462L frame shift STOP 20), exon5, Chr.D1.

Medical system: Skeletal

Breeds: Domestic Cat shorthaire

Age of onset of symptoms: By 3 months of age

Vitamin D dependant rickets (VDDR) type IB is a metabolic bone disorder caused by the body’s inability to properly activate vitamin D, even when diet and sun exposure are normal. Because vitamin D is essential for intestinal calcium absorption, affected animals develop poor bone mineralization, particularly pronounced during periods of rapid growth.  A three-month-old domestic shorthaired cat presented with lethargy, seizures and pain. Hypocalcemia and skeletal demineralisation were observed, and vitamin D dependant rickets was suspected.  The CYP2R1 gene codes for one of the key proteins in the activation of vitamin D.  Sequencing the CYP2R1 gene of the affected cat revealed a homozygous single nucleotide deletion in exon5 that could be responsible for the clinical presentation.  The cat responded to calcitriol (vitamin D3) treatment. No additional screening of cat populations was performed, such that frequencies of the mutation remain unknown, which may warrant further investigation. VDDR remains a very rare disease in the cat which should be considered only when other more common causes of hypocalcemia and skeletal demineralisation have been ruled out.

References:

OMIA link: [2221-9685]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Teshima T, Kurita S, Sasaki T, et al. (2019) A genetic variant of CYP2R1 identified in a cat with type 1B vitamin D-dependent rickets: a case report. BMC Vet Res. 15(1):62. [pm/30777056]

Bauer TR, Pratt SM, Palena CM, et al. (2017) Feline leukocyte adhesion (CD18) deficiency caused by a deletion in the integrin β2 (ITGB2) gene. Vet Clin Pathol 46:391-400.  [pm/28750142]

Contributed by: Salim El Moustaghfir and Yihu Tang, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).