The MCT8 thyroid hormone transporter and Allan–Herndon–Dudley syndrome

Thyroid hormone is essential for the proper development and function of the brain. The active form of thyroid hormone is T3, which binds to nuclear receptors. Recently, a transporter specific for T3, MCT8 (monocarboxylate transporter 8) was identified. MCT8 is highly expressed in liver and brain. The gene is located in Xq13 and mutations in MCT8 are responsible for an X-linked condition, Allan–Herndon–Dudley syndrome (AHDS). This syndrome is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays. Affected males also present with muscle hypoplasia, generalized muscle weakness, and limited speech. Importantly, these patients have elevated serum levels of free T3, low to below normal serum levels of free T4, and levels of thyroid stimulating hormone that are within the normal range. This constellation of measurements of thyroid function enables quick screening for AHDS in males presenting with cognitive impairment, congenital hypotonia, and generalized muscle weakness.