What is MCT8 deficiency?

Allan-Herndon-Dudley syndrome (AHDS) — also known at MCT8 deficiency — is a rare genetic disorder that affects a child’s cognition, mobility and overall health. In individuals with AHDS, thyroid hormone is unable to enter cells in the brain because of a defect in a thyroid hormone transporter called MCT8. Thyroid hormones are particularly important for proper brain development during pregnancy and early childhood.

At the same time, excess thyroid hormone, specifically T3 (triiodothyronine), enter tissues in the rest of the body, which typically leads to life-threatening complications. The result is that patients are born with permanent and severe developmental delay from hypothyroidism (not enough thyroid hormone) in the brain while at the same time they experience hyperthyroidism (too much thyroid hormone) in the rest of their body, leading to intellectual disability, decreased muscle tone, disorganized movements, restless sleep, increased heart rate (tachycardia), failure to thrive/inability to gain weight, and, ultimately, severe infection and cardio-respiratory failure.

AHDS is an X-linked genetic disorder with a 50% chance that male babies will have the disorder if their mother is a carrier of the abnormal gene that codes for the MCT8 thyroid hormone transporter protein. Although not well described, female carriers of the MCT8 gene may also have symptoms, often more mild although several females have had more severe symptoms similar to males. The disorder may also develop spontaneously during fetal development, where the baby is the first person in the family to have AHDS.

Signs and symptoms of MCT8 deficiency

There are several signs/symptoms of MCT8 deficiency. They include:

• Appearance – Patients may have a longer and more narrow face compared to other family members. Patients may also have spine (scoliosis) and chest (pectus excavatum) abnormalities.
• Developmental delay/severe intellectual disability resulting in an impaired ability to speak, inability to walk, etc.
• Hypotonia (low muscle strength) with stiffness to the legs (spasticity)
• Involuntary, disorganized and abnormal muscle movements that have short and repeated bursts of increased intensity that may increase during physical contact. As adults, patients may have contractures, decreased range of motion of joints.
• Failure to thrive/poor weight gain and malnutrition
• Increased heart rate (tachycardia) and abnormal heartbeat (arrhythmia)

Causes of MCT8 deficiency

MCT8 deficiency is caused by a genetic mutation in the SLC16A2 gene. This gene provides the instructions that make a protein called monocarboxylate transporter 8 (also known as MCT8). The MCT8 protein is a channel that allows thyroid hormones, most importantly T3, to move from the blood stream into cells of the brain. In the rest of the body, MCT8 is not required for movement of T3 into the cells.

Testing and diagnosis of MCT8 deficiency

Males with developmental delay, decreased muscle tone, increased resting heart rate and poor weight gain should have a blood test to measure the level of the thyroid hormone called T3 (liothyronine) along with a thyroid stimulating hormone (TSH) and T4 (thyroxine).

An elevated T3 with a normal thyroid stimulating hormone (TSH) and low normal T4 level is consistent with the diagnosis of AHDS.

A blood test looking for a genetic mutation (an abnormality in the coding of our DNA) in the SLC16A2 gene should also be performed to confirm the diagnosis. A specialist involved in caring for patients with AHDS, a pediatric neurologist or endocrinologist, along with a geneticist and genetic counselor should be involved in educating the family in the process and meaning of finding a genetic mutation that can be passed between generations of other family members.

Treatment of MCT8 deficiency

There is no known cure for MCT8 deficiency at this time, although there is on-going research using different forms of thyroid hormone that do not require the MCT8 to enter the cells of the brain. The names of some of these investigational drugs include TRIAC (also called tiratricol, Teatrois or Emcitate) and DITPA.

One of the major challenges is that the damage to the brain starts during pregnancy, so, ideally, treatment to help decrease the damage would be started in the first trimester of pregnancy. Unfortunately, the diagnosis for most patients does not happen until months to years after the baby is born. Once the damage to the brain occurs, it cannot be fixed. Because the brain undergoes the greatest growth and development during the first three years of life, it is believed that the earlier the use of these drugs the greater the potential benefit.

The goal of this research is to try to identify babies as early as possible in an effort to decrease the severity of developmental delay and decreased muscle tone as well as improve increased heart rate and poor weight gain.

There are very few hospitals in the world with experience treating patients with AHDS. Children’s Hospital of Philadelphia (CHOP) is one of two hospitals in the United States involved in international research for MCT8 deficiency. Similar to other rare medical diagnoses, finding a hospital with the most experience, including being involved in clinical trials, is ideal, when possible.

Follow-up care of MCT8 deficiency

Patients with MCT8 deficiency are best cared for by a multidisciplinary team, often including providers from endocrinology, genetics, neurology, physical therapy, occupational therapy, speech therapy, social work and potentially others. Follow-up care will include appointments and visits with individuals from all these fields. It is important to find experts and care teams who are familiar with this disorder because it is so rare.

Patients may need a gastronomy tube (G-tube) to optimize the intake of calories and weight gain.

Long-term outlook for MCT8 deficiency

Patients diagnosed with MCT8 deficiency have a varying severity of symptoms. Life expectancy may also vary; even with excellent care, many patients experience a shortened lifespan due to  malnutrition and overwhelming infections.

Patients diagnosed with MCT8 deficiency require extensive care, either from primary caregivers or from assisted living facilities. Most children will live into young adulthood but will never develop the ability to walk independently or talk with others and will rely on caregivers for daily activities such as feeding, bathing, hygiene, getting dressed, transportation/movement, and administration of medications and other forms of support.

Providers at Children’s Hospital of Philadelphia who treat MCT8 deficiency

• Andrew Bauer, MD, Division of Endocrinology & Diabetes
• Adeline Vanderver, MD, Division of Neurology
• Sam Pierce, Physical Therapy

Additional resources

• MCT8-AHDS Foundation
• National Organization for Rare Disorders