General description

MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome, is a rare X-linked recessive disorder predominantly affecting males. The condition is caused by mutations in the SLC16A2 gene, which encodes the MCT8 protein - a crucial thyroid hormone transporter. This protein plays an essential role in neurogenesis, neuronal migration, and myelination by facilitating the transport of thyroid hormones across the blood-brain barrier.

Affected individuals typically show no problems during the perinatal period but develop significant neurological issues early in life. Clinical features include severe global developmental delay, intellectual disability, persistent primitive reflexes, poor head control, and hypotonia in infancy that progresses to increased muscle tone in the limbs and trunk. Many patients develop dystonia, choreoathetosis, paroxysmal movement disorders, and pyramidal signs. Most affected males never acquire speech or develop motor milestones.

The condition presents with a distinctive thyroid hormone profile characterized by high free T3, low free and total T4, but normal TSH levels. Despite normal TSH, there is central hypothyroidism because MCT8 is essential for thyroid hormones to cross the blood-brain barrier. Diagnosis can be challenging as the condition may be misdiagnosed as athetoid cerebral palsy, particularly when MRI findings are subtle. Without specific thyroid function testing, the diagnosis may be missed entirely.