MCT8 - AHDS

The Allan-Herndon-Dudley syndrome (AHDS) is a very rare form of developmental disorder that involves severe mental and physical limitations. The cause of the AHDS can be found in mutations in the SLC16A2 gene (also called the MCT8 gene). MCT8 transports thyroid hormones (T3 and T4) from the blood into cells where the hormones can work. Thyroid hormones include essential importance during embryonic and postnatal brain development. If the transporter is mutated, it leads to a disturbed uptake of the thyroid hormone into the brain, so that its maturation is severely impaired.The effects of the hormone deficiency are so severe that 95% of those affected can not speak and are unable to control their muscle movements. The affected persons cannot sit, stand or walk independently.

The target of our Foundation is to help treating the developmental disorders and neurological symptoms of these patients.

Symptoms

Affected children stand out early due to extreme muscle weakness (hypotension) and underdeveloped muscles. Most children cannot turn on their own or hold their heads upright. Later, joint deformities and contractures can occur, leading to additional impaired mobility, as well as muscle cramps and involuntary movements of the arms and legs. Those affected also suffer from severe intellectual developmental delays that are so significant that they are usually unable to learn to speak. Later side effects that appear are respiratory diseases, in part epilepsy.

Diagnosis

In laboratory terms, increased T3 levels at normal FT4 and TSH levels indicates Allan-Herndon-Dudley syndrome. Despite increased T3 levels, the hormone cannot be transported to the brain due to the mutations in MCT8. The muscle, on the other hand, has other thyroid hormone transporters that can transport thyroid hormones into the muscle cell independently of MCT8. It is assumed that the muscle cell is exposed to an overdose of T3, which would lead to its own degradation and thus cause the muscle weakness. The prognosis for patients with Allan-Herndon-Dudley syndrome is relatively unfavorable. So far, the disease is incurable.

Treatment

The AHDS is a causally untreatable disease. At the present time there is no standardized treatment option for patients with AHDS even in the field of symptomatic therapy. Treatment approaches are concerned with the thyroid hormone derivative TRIAC (Triiodothyroacetat). TRIAC is transported MCT8-independent in cells and acts within the cell via the same mechanism as T3. Clinical studies showed that children were able to keep their heads independently, whose TRIAC treatment started at a very early stage of development (immediately after birth). In the cognitive or motor area, however, no noteworthy successes have been recorded so far - possibly because the therapy has been started too late.