Clinical and Endocrine Features of Two Allan-Herndon-Dudley Syndrome Patients with Monocarboxylate Transporter 8 Mutations

The monocarboxylate transporter 8 (MCT8) gene, located on chromosome Xq13.2, encodes a thyroid hormone transporter that is involved in triiodothyronine (T3) uptake into central neurons. MCT8 mutations cause an X-linked syndromic disorder known as Allan-Herndon-Dudley syndrome (AHDS) that is characterized by severe psychomotor delays, abnormal thyroid function, and hypomyelinated leukodystrophies. We identified 2 AHDS patients with developmental delays, truncal hypotonia, and spastic paraplegia. These patients presented with psychomotor retardation and characteristic thyroid function abnormalities, such as elevated T3 and low T4 levels. Direct MCT8 sequencing identified heterozygous mutations in each patient: p.I114N and p.A224V, respectively. Because it is difficult to suspect AHDS solely according to neurological features, thyroid function, including the T3 level, should be screened in male patients with X-linked mental retardation. Although the clinical features of hypothyroidism cannot be improved by only administering levothyroxine treatment, early diagnosis, management, and appropriate genetic counseling should be provided to at-risk families. (C) 2015 S. Karger AG, Basel