Thyroid hormones are known to be essential for growth, development and 
metabolism. Recently mutations in the SLC16A2 gene coding for the 
monocarboxylate thyroid hormone transporter 8, MCT8, have been associated with 
Allan-Herndon-Dudley syndrome (AHDS), 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 in a boy affected by AHDS with severe neurological abnormalities and a 
novel de novo SLC16A2 gene insertion, 1343-1344insGCCC, resulting in a truncated 
protein lacking the last four transmembrane domains (TMDs) as well as the 
carboxyl cytoplasmic end. He presents mental retardation, axial hypotonia, 
hypertonia of arms and legs, paroxysmal dyskinesias, seizures. The endocrine 
phenotype showed low serum total and free thyroxine (T4), very elevated total 
and free triiodothyronine (T3) and normal thyrotropin (TSH) with blunted 
response to thyrotropin-releasing hormone (TRH). The latter finding was 
unexpected and suggested that the lack of functional MCT8 was counterbalanced at 
the thyrotrope cell level by high serum T3 concentration and/or by increased 
intrapituitary type 2 deiodinase (D2) activity. Our case constitutes a relevant 
contribution to better characterize this disorder and to elucidate the 
functional consequences of SLC16A2 gene mutations.