ELEVATED SERUM T3 IS A MARKER FOR X-LINKED MENTAL RETARDATION/”CEREBRAL PALSY” SYNDROME CAUSED BY MUTATION IN MONOCARBOXYLATE TRANSPORTER-8

Objectives: Monocarboxylate transporter-8 (MCT-8) is a transporter of the thyroid hormones T3 and T4, and it was recently shown that mutation of this gene causes an X-linked mental retardation / “cerebral palsy” (MR/CP) syndrome with severe motor compromise and abnormal thyroid hormones profile, with inappropriate elevated T3 and normal or elevated TSH. This condition is allelic to Allan-Herndon-Dudley syndrome, one of the recognized causes of X-linked mental retardation but its clinical features are closer to what is seen in severe dystonic cerebral palsy. The purpose of this presentation is to report clinical and laboratorial features of a family with MCT-8 mutation.

Methods: This study consists of clinical and biochemical evaluation as well as mutation analysis of MCT-8 gene in a family with an X-linked MR/CP syndrome.

Results: We evaluate a multigenerational family with 4 affected individuals, ages ranging from 24 to 62 years, with an X-linked MR/CP syndrome characterized by: 1. early onset developmental delay; 2. very slowly progressive dystonia, with deterioration of ability of head or sitting control; 3. profound mental retardation with lack of speech and communication ability; 4. muscular wasting and progressive contractures. MCT-8 mutation analysis detected a c.1834delC that causes a frameshift change and creates a novel stop codon at nucleotide 196 of the 3'UTR. Thyroid function studies disclosed, in all affected individuals, elevated T3 and free T3 and normal values of T4 and TSH. No clinical symptom characteristic of classic hypothyroidism was present.

Conclusion: It is recommended to evaluate thyroid function, including T3, in males with severe mental retardation and dystonic “cerebral palsy” with slowly progressive contractures and reduction of motor abilities. Survival in males carrying MCT-8 mutations can be very long, as demonstrated in this study.