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Hereditary Vitamin D-Resistant Rickets (HVDRR)
| Acronym: | HVDRR |
| Gene: | VDR |
| Mutation: | c.462delG |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Hereditary Vitamin D-Resistant Rickets (HVDRR) is a hereditary disorder affecting the Pomeranian dog breed, caused by insufficient vitamin D intake. Generally, canine rickets can be divided into two forms, type I and type II. In type I Vitamin D-dependent rickets, a renal enzyme needed for vitamin D conversion is inactive, while in type II vitamin D-resistant rickets there is an end-organ resistance to the active hormone. The form of hereditary vitamin D-resistant rickets which if affecting Pomeranians belongs to the group type II. The disorder is characterized by hypocalcemia, secondary hyperparathyroidism, hypomineralization of bone rickets, and in some cases alopecia.
In the HVDRR-affected dogs, the intestinal absorption of calcium is insufficient to meet the calcium demands of a growing skeleton. The first symptoms appear early, around 4 months of age when the puppy seems to tire easily when playing. Physical examination reveals lateral bowing of both forelimbs and thickening of the distal radii. With time, alopecia is becoming more generalized. Serum analysis shows hypocalcemia, as well as hyperphosphatemia and increased alkaline phosphatase. Radiography shows decreased mineralization. Based on results which are revealing hypocalcemia, hyperparathyroidism, and skeletal abnormalities, veterinarians can diagnose a vitamin D-dependent form of rickets. Treatment with oral calcium supplementation was relatively inefficient, because total serum calcium levels were persistently low, despite a consistent increase in oral calcium supplementation doses. Altogether, clinical signs include hypocalcemia, secondary hyperparathyroidism, joint pain, lameness, bone malformations, alopecia, spontaneous fractures, and limb deformities. Due to spontaneous fractures, which can occur anywhere in the body, affected dogs are commonly euthanized upon owners’ request.
Hereditary Vitamin D-Resistant Rickets (HVDRR) in Pomeranians is caused by a mutation in the VDR gene. HVDRR is inherited as an autosomal recessive disorder. Healthy parents of an affected dog are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
LeVine DN, Zhou Y, Ghiloni RJ, Fields EL, Birkenheuer AJ, Gookin JL, Roberston ID, Malloy PJ, Feldman D. (2009) Hereditary 1,25-dihydroxy vitamin D-resistant rickets in a Pomeranian dog caused by a novel mutation in the vitamin D receptor gene. J Vet Intern Med 23:1278-83.