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Congenital Hypothyroidism (TPO Gene, Spanish Water Dog)

Congenital Hypothyroidism (TPO Gene, Spanish Water Dog)

Hypothyroidism in dogs is an endocrine disease that occurs when the thyroid gland does not produce enough thyroid hormones, mainly thyroxine (T4) and triiodothyronine (T3). These hormones are crucial for the maintenance of metabolism and the overall functioning of the body. In congenital hypothyroidism the hormone deficiency is present from birth.

Symptoms

Congenital hypothyroidism in dogs that manifests with an enlarged thyroid (goiter) produces very early onset symptoms (around the first week) such as lethargy, susceptibility to infections, growth retardation and feeding problems. There is a delay in tooth eruption, opening of the eyes and ear canals, as well as alterations in skin and coat growth. In severe cases, puppies may show neurological symptoms such as incoordination and muscle weakness. If left untreated, the disease can be lethal for puppies, so early detection is essential.

Disease Management

Treatment consists of increasing or replacing the missing thyroid hormone. Thyroxine (T4) is the most commonly used replacement thyroid hormone in dogs and drug treatment with levothyroxine is generally lifelong. Periodic checks are usually performed to adjust the dose and once hormone levels have stabilized, annual follow-up tests are performed. If puppies with hypothyroidism are treated early (between 3 and 4 months of age) it is usually possible to reverse the symptoms and have a normal development. If you suspect that your puppy may have congenital hypothyroidism, it is important to consult a veterinarian for diagnosis and appropriate treatment.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Congenital hypothyroidism in humans can be caused by mutations in multiple genes such as DUOX2, PAX8, SLC5A5, TG, TPO, TSHB and TSHR. In dogs, causative mutations have been identified in the TPO gene that codes for the enzyme thyroid peroxidase which is key in the biosynthesis of the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine), as it catalyzes the oxidation of iodine and its incorporation into thyroglobulin, a protein that is stored in the thyroid gland and contains thyroid hormones in the form of precursors. In the case of the Spanish Water Dog breed, a variant (c.39_40insG) has been identified that consists of the insertion of a guanosine (G) in the first exon of the cDNA of the TPO gene, which causes a shift in the reading frame of translation. This modification causes the appearance of an early stop codon that results in the truncation of the protein with peroxidase activity.

Most affected breeds

French Bulldog
Scottish Wolfhound
Spanish Water Dog
Giant Schnauzer
Tenterfield Terrier
American Mouse Terrier
Toy Fox Terrier

Bibliography

Bianchi M, Dahlgren S, Massey J, et al. A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12. PLoS One. 2015 Aug 11;10(8):e0134720.

Fyfe JC, Lynch M, Olsen J, et al. A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure. Mamm Genome. 2013 Apr;24(3-4):127-33.