Loss of MCT8 function causes Allan-Herndon-Dudley syndrome (AHDS, OMIM 300523) characterized by severe intellectual and motor disability due to cerebral hypothyroidism.
Therefore, sobetirome and Sob-AM2 have the potential to address the cerebral hypothyroidism and the peripheral hyperthyroidism characteristic of MCT8 deficiency.
A three-and-a-half-year-old male with clinical and biochemical AHDS phenotype and a history of normal neonatal screening for hypothyroidism underwent SLC16A2 molecular analysis.
Mutations in the gene encoding the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), cause mental retardation in humans associated with a specific thyroid hormone phenotype manifesting high serum T3 and low T4 and rT3 levels.
Heterozygous MCT8 women should be monitored for requirement of l-T₄ therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia.
We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T(3) transporters become hyperthyroid, if they are exposed directly to the high plasma T(3).
Mutations of the X-linked thyroid hormone (TH) transporter (monocarboxylate transporter, MCT8) produce in humans unusual abnormalities of thyroid function characterized by high serum T3 and low T4 and rT3.