MCT8

MCT8, or monocarboxylate transporter 8, is a membrane transporter encoded by the SLC16A2 gene. It belongs to the monocarboxylate transporter family and is expressed in several tissues, with notable presence at the blood-brain barrier and in brain cells, as well as in liver and other organs. MCT8 is specialized for transporting thyroid hormones, particularly triiodothyronine (T3) and thyroxine (T4), into cells and across the blood-brain barrier, enabling thyroid hormone supply to neurons during development.

Mutations in SLC16A2 cause Allan-Herndon-Dudley syndrome, an X-linked neurodevelopmental disorder. The condition is characterized by severe motor and cognitive impairment beginning in infancy, profound hypotonia, spasticity, and movement disorders, often with dysphagia and feeding difficulties. Brain development is compromised because neurons receive insufficient thyroid hormone, while peripheral tissues can show a thyrotoxic profile.

Biochemically, affected individuals typically have markedly elevated serum T3, reduced T4, and variable TSH levels. The pattern reflects a combination of impaired brain thyroid hormone uptake and peripheral thyroid hormone disturbances. Diagnosis is suggested by the clinical and biochemical profile and confirmed by genetic testing for SLC16A2 mutations.

There is no cure. Management is supportive and multidisciplinary, focusing on rehabilitation and management of complications. In some cases, thyroid hormone analogs such as Triac (3,3',5-triiodothyroacetic acid) have shown potential to improve outcomes by bypassing some transport limitations and entering the brain via alternative pathways, especially when started early. Ongoing research seeks additional therapies, including targeted pharmacological approaches and gene therapy. The prognosis remains poor in untreated individuals, with lifelong motor and developmental impairment.