THINK, TALK, TEST FOR MCT8 DEFICIENCY
MCT8 deficiency is a rare but life-shortening disease with obvious symptoms such as hypotonia and lack of head control, i.e. a floppy head. We are dedicated to advancing awareness and education to improve the situation for those affected by MCT8 deficiency. This site is primarily for healthcare professionals.
MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome (AHDS), is a rare disease caused by inactivating mutations in the SLC16A2 gene that encodes monocarboxylate transporter 8 (MCT8)1. MCT8 is a transmembrane transporter, specific for the thyroid hormones T3 and T4. MCT8 is the only transporter for T3 and T4 in the brain, whereas additional transporters exist for these hormones in other tissues and organs1,2. Thyroid hormones are normally precisely regulated throughout the body and a functional MCT8 is critical to this regulation1,2
Etiology and symptoms
- MCT8 deficiency leads to severe brain hypothyroidism due to impaired transport of thyroid hormones across the blood-brain barrier causing serious neurological issues such as lack of neurocognitive development in childhood1
- The lack of thyroid stimulation in the brain causes the hypothalamic–pituitary–adrenal axis to increase thyroid hormone production.1,3 The high concentrations of T3 outside the brain, in MCT8-independent tissues, causes a state of chronic thyrotoxicosis manifested by weight loss, muscle wasting, impaired motor skills, cardiovascular impairment (chronic tachycardia and high blood pressure), anxiety and sleep problems2,3
- On top of the thyrotoxicosis related symptoms, MCT8 deficiency cause neurodevelopmental delay and impaired motor function, which in most of those affected results in inability to maintain head control, sit independently and walk2,3,4
Consequences - As well as significant morbidity, MCT8 deficiency significantly affects mortality with median overall survival at just 35 years2
- 30% of patients die during childhood2
- Pulmonary infection and sudden death are the main causes of death2
- MCT8 deficiency patients require 24h, life-long care
Tissues relying on MCT8 for thyroid hormone transport are relatively hypothyroid, whereas tissues that are independent of MCT8 are in a thyrotoxic state, caused by the increased serum T3 concentrations (TH = thyroid hormone, PACs = premature atrial complexes, SHBG = sex hormone binding globulin, CK = creatine kinase, BMI = body mass index)
For more reading, please click on the references below
- While incidence has been previously estimated at 1 in 70,000 new-born males, a screening study suggests prevalence could be higher at 1 in 50,0001
- While there are no immediate symptoms in the newborn apart from potential hypotonia, obvious signs like a floppy head do appear within the first few months and these manifestations will prevail into adulthood without effective treatment
- Patients who cannot attain head control by 1.5 years or being underweight at a young age are at an increased risk of death2
- A large proportion of MCT8-deficient patients may have evaded diagnosis and would benefit from being properly diagnosed
- A recent study highlights the major delays that currently exist in diagnosing this disease2
- In patients with MCT8 deficiency, there are very high levels of T3, low to normal T4 and slightly elevated TSH1-3
- MCT8 deficiency can be diagnosed by an inexpensive and simple T3 test that can be followed by a confirmatory genetic test
By diagnosing patients as early as possible, there is a possibility to support those affected with the best available care4
- Martinez CG et al. Frontiers in Neuroscience 2020; 14: 380.
- Groeneweg S et al. Lancet Diab Endocrinol 2020; 8: 594-605.
- Groeneweg S et al. Lancet Diab Endocrinol 2019; Published online, July 31, 2019 http://dx.doi.org/10.1016/S2213-8587(19)30155-X.
- Van Geest FS et al. Endocrine 2021; 71:689-695; Published online , March 1, 2021 https://doi.org/10.1007/s12020-020-02603-y