Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter

Thyroid hormones are known to be essential for growth, development, and metabolism. Recently, the monocarboxylate transporter 8 (MCT8) was identified as a thyroid hormone transporter, and MCT8 mutations have been associated with Allan-Herndon-Dudley syndrome, an X linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. Here we describe in detail the clinical and biochemical features and the response to thyroid hormone (L-thyroxine (LT4)) administration in a boy with an MCT8 mutation (c.1649delA) that truncates the protein in the twelfth transmembrane domain. It is of note that brain magnetic resonance imaging (MRI) revealed delayed myelination from infancy. Endocrine functions other than thyroid hormone regulation and metabolism were intact, resulting in normal hypothalamic/pituitary function tests. While LT4 administration suppressed thyrotropin (TSH) secretion, no significant changes in thyroid hormone values or clinical symptoms were observed. Conclusion: the characteristic thyroid hormone function tests and brain MRI findings may allow screening of high-risk populations for a better understanding of MCT8 pathophysiology.