In other species: domestic cat , horse , mule

Categories: Endocrine / exocrine gland phene (incl mammary gland)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 145000 (trait) , 145001 (trait) , 239199 (trait) , 239200 (trait) , 256120 (trait) , 600166 (trait)

Links to MONDO diseases:

• MONDO:0001741: hyperparathyroidism

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Key variant is published: no

Cross-species summary: Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It may be primary or secondary; primary hyperparathyroidism is caused by parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, and multiple endocrine neoplasia. It is associated with hypercalcemia and hypophosphatemia. ... Secondary hyperparathyroidism is caused by the chronic stimulation of the parathyroid glands in patients with chronic renal failure, rickets, and malabsorption syndromes. [NCIT:C48259]

Species-specific name: This entry includes information about primary hyperparathyroidism (PHPT)

Species-specific description: This disorder occurs in many different forms, many of which are not inherited. Goldstein et al. (2008) report that the majority of cases of primary hyperparathyroidism in dogs are due to adenoma, and that malignant parathyroid carcinoma are considered rare. Breed predispositions have been reported and a neonatal form of hyperparathyroidism with a suspected autosomal recessive mode of inheritance has been reported in German Shepherd puppies (Thompson et al., 1984) and inherited hyperparathyroidism with adult onset and a suspected autosomal dominant mode of inheritance has been reported in Keeshond (Goldstein et al., 2007). A non-published DNA test is offered for Keeshond.

Inheritance: Genetic forms of primary hyperparathyroidism include a suspected recessive form with early onset in German Shepherd puppies (Thompson et al., 1984) and an autosomal dominant form with adult onset in Keeshond (Goldstein et al., 2007).

Molecular basis: A DNA test for the disorder in Keeshond is included in the OFA's list at https://ofa.org/all-dna-tests/, which directs enquiries to the Animal Health Diagnostic Center at Cornell University: https://www.vet.cornell.edu/animal-health-diagnostic-center/testing/protocols/primary-hyperparathyroidism. The molecular basis has not been published (American Kennel Club Canine Health Foundation, 2021).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Across genetic and non-genetic forms of the disease, the most common clinical signs associated with canine hyperparathyroidism include polyuria (Thompson et al., 1984; Gear et al.. 2005; Sakals et al., 2010; Jores and Kessler, 2011), polydipsia (Thompson et al., 1984; Gear et al., 2005; Sakals et al., 2010; Jores and Kessler, 2011) stiff gait (Jores and Kessler, 2011) and weakness (Thompson et al., 1984; Sakals et al., 2010). Less common clinical signs include anorexia (Sakals et al., 2010), stunted growth (Thompson et al., 1984) and reduced activity (Jores and Kessler, 2011). Changes in haematology and biochemistry have been noted, with many published case reports indicating mild to extensive hypercalcaemia (Thompson et al., 1984; Sakals et al., 2010; Jores and Kessler, 2011), hypophosphatemia (Thompson et al., 1984; Jores and Kessler, 2011) and elevated serum parathyroid hormone (Sakals et al., 2010; Jores and Kessler, 2011) to be the key changes associated with canine hyperparathyroidism. IT thanks DVM student Stephanie Shields, who provided the basis of this contribution in May 2023.

Pathology: Reported pathological findings are focused on the appearance of neoplastic lesions within the parathyroid gland/s, with the key diagnostic feature being nodular enlargement of the parathyroid gland (Gear et al., 2005). A study relating to a genetic form of the disease with early onset also noted reduced bone density (Thompson et al., 1984) using radiographs, likely as a result of calcium mobilisation from bones due to elevated serum parathyroid hormone in individuals with hyperparathyroidism. IT thanks DVM student Stephanie Shields, who provided the basis of this contribution in May 2023.

Breeds: German Shepherd Dog (Dog) (VBO_0200577), Keeshond (Dog) (VBO_0200759).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below