Congenital hypothyroidism (TPO gene, various breeds)

Congenital hypothyroidism is a condition that occurs after birth, characterized by dwarfism and problems in mental development due to a deficiency in the production of thyroid hormones. The affected gene, TPO, encodes an enzyme crucial for the synthesis of these thyroid hormones.

Symptoms

Newborn cats are usually of normal weight, but the first signs of growth retardation usually appear between the third and eighth week of life, eventually leading to disproportionate dwarfism. Because of the importance of thyroid hormones in the development of the nervous system, affected cats also experience impaired mental status. Other symptoms include delayed dental eruption, possible development of goiter and distinctive physical features such as large skull, shortened ears, square trunk and short limbs and neck. In addition, they may manifest constipation, obesity, anorexia, hypothermia, lethargy and persistent juvenile coat.

Disease Management

The management of congenital hypothyroidism focuses on the administration of hormone replacement therapy to normalize thyroid hormone levels. Levothyroxine sodium is the standard treatment, given for life to compensate for thyroid insufficiency. In cases with goiter, it may be necessary to evaluate the need for surgical intervention.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, 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 cat 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 cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Congenital hypothyroidism, also known as thyroid dyshormonogenesis, is an endocrine disorder present in several animal species, including cats. This disorder affects the production of thyroid hormones, which are crucial for regulating metabolism, growth and development. A genetic variant has been identified in several breeds of cats, such as the British Shorthair, domestic short, medium and long-haired, and Russian Blue, associated with congenital hypothyroidism in the TPO gene. This gene encodes the thyroid peroxidase enzyme necessary for the synthesis of thyroid hormones. The specific variant is a missense mutation c.430G>A (p.Gly144Arg), which affects a crucial functional region of the TPO protein, interfering with the correct organification of iodine. This mutation has been found in multiple breeds, suggesting that the incidence of this disease in cats may be underestimated due to high undiagnosed neonatal mortality.

Most affected breeds

Domestic Shorthair
Domestic Longhair
British Shorthair
Russian Blue

Bibliography

Bojanic K, Acke E, Jones BR. Congenital hypothyroidism of dogs and cats: a review. N Z Vet J. 2011 May