The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome

Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):307-21. doi: 10.1016/j.beem.2007.03.009.

Abstract

Thyroid hormone is essential for the proper development and function of the brain. The active form of thyroid hormone is T(3), which binds to nuclear receptors. Recently, a transporter specific for T(3), MCT8 (monocarboxylate transporter 8) was identified. MCT8 is highly expressed in liver and brain. The gene is located in Xq13 and mutations in MCT8 are responsible for an X-linked condition, Allan-Herndon-Dudley syndrome (AHDS). This syndrome is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays. Affected males also present with muscle hypoplasia, generalized muscle weakness, and limited speech. Importantly, these patients have elevated serum levels of free T(3), low to below normal serum levels of free T(4), and levels of thyroid stimulating hormone that are within the normal range. This constellation of measurements of thyroid function enables quick screening for AHDS in males presenting with cognitive impairment, congenital hypotonia, and generalized muscle weakness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / metabolism*
  • Abnormalities, Multiple / therapy
  • Amino Acid Sequence
  • Brain / drug effects
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / metabolism
  • Genetic Diseases, Inborn / therapy
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism
  • Male
  • Models, Biological
  • Molecular Sequence Data
  • Monocarboxylic Acid Transporters / metabolism
  • Monocarboxylic Acid Transporters / physiology*
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / metabolism*
  • Muscle Weakness / genetics
  • Muscle Weakness / metabolism
  • Symporters
  • Syndrome
  • Thyroid Hormones / metabolism
  • Thyroid Hormones / pharmacology

Substances

  • Monocarboxylic Acid Transporters
  • SLC16A2 protein, human
  • Symporters
  • Thyroid Hormones