TPO

Congenital hypothyroidism

TPO gene mutations can cause congenital hypothyroidism, a condition characterized by abnormally low levels of thyroid hormones starting from birth. The TPO gene mutations involved in this condition delete, add, or change DNA building blocks (base pairs) in the TPO gene. Some mutations lead to an abnormally small thyroid peroxidase enzyme that breaks apart before it can be inserted into the cell membrane. Other mutations change the enzyme's 3-dimensional shape, preventing it from functioning properly within the cell membrane. Without functional thyroid peroxidase, iodine taken up by the thyroid gland is not added to thyroglobulin. As a result, the production of thyroid hormones is absent or reduced, leading to the features of congenital hypothyroidism. In most affected individuals, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production. Because cases caused by TPO gene mutations result from a disruption of thyroid hormone synthesis, they are classified as thyroid dyshormonogenesis.