Thyroid Research Thyroid Research Archive Congenital

Mutations in a thyroid hormone–transport molecule cause neurologic and thyroid abnormalities

(March 2004)

The background of the study. Thyroxine (T4) and triiodothyronine (T3) enter cells to regulate gene function. Entry is facilitated by transporter molecules located in the outer membrane of the cells. This study describes the results of clinical and molecular studies of two families with mutations of the gene for a transporter molecule, known as MCT8.

Family 1. The first patient was an 8-year-old boy who had the onset of muscle dysfunction, irritability, and poor feeding within days after birth. His subsequent development was markedly delayed; at age 2 years he could not sit, crawl, or speak, and he later became quadriplegic. At age 17 months, he had mild hypothyroidism; he was treated with T4, with no benefit. His mother had a slightly high serum thyrotropin (TSH) value. His father, only sibling (a boy), and other maternal relatives were normal.

Family 2. The patient in this family was a 3-year-old boy who at neonatal screening was thought to have mild hypothyroidism, which was treated with T4. At age 3 months, he had feeding problems, abnormal eye movements, and hypertonic muscles, and then quadriplegia. His mother, a maternal aunt, and the maternal grandmother also had mild hypothyroidism, and a maternal uncle had died at age 10 years with cerebral palsy and severe developmental delay.

Molecular studies. Analysis of the MCT8 gene, located on the X chromosome, revealed different mutations in the two patients, each likely to cause loss of function in the transporter, and their mothers.

The conclusions of the study. Mutations in the X-linked MCT8 gene, which carry T4 and T3 into cells, results in severe developmental delay and neurologic abnormalities in affected males.

The original article. Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 2004;74:168-75.

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Congenital Hypothyroidism

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