Physical therapy is very important; massaging of muscles is also good as it tends to decrease tension and allow the therapy to be more effective.
MCT8 Deficiency also referred to as Allan-Herndon-Dudley syndrome is an X-link syndrome that only affects boys. In 1944 the first case of MCT8 deficiency was reported. It took 60 years of research to understand that the syndrome is caused by mutations in the monocarboxylate transporter (MCT8). The SLC16A2 gene is the blueprint for the formation of the MCT8 thyroid hormone transporter. While there are several different transporters that fulfill this function, MCT8 is required for the efficient entry of these hormones into the brain. Thyroid hormones are important in the development of brain function particularly in the embryo, infant and child life. Because the SLC16A2 gene is located in the X chromosome, the syndrome affects only boys. While girls may be carriers, it is extremely rare that they may exhibit symptoms.
Either a Pediatric Neurologist (due to the fact that it involves mental and motor delay) or Pediatric Endocrinologist (due to the fact that thyroid hormone tests abnormalities are characteristic for the syndrome)
There is an estimated number of 320 diagnosed patients all over the world (Orpha.net). However, certain studies have shown that up to 4% of the undiagnosed cases of children with mental and motor delay may be affected by this syndrome.
AHDS or MCT8 Deficiency is the name that covers all mutations of the MCT8 transporter. In one third of cases the same mutation is present in a child from another unrelated family. Some mutations are inherited from the mother (X-link) some others, called “de novo”, are new.
There are three situations:
- When the mutation is inherited – the mother is a carrier of the mutation (blood tests may show she is a carrier). This is an X-link inherited mutation.
- When the mutation is spontaneous – also called “de novo”. This means that the mutation has developed in the egg.
- In very rare cases, the mutation may be present in the mother but only in specific tissues. In that case, the mother is a “mosaic-carrier” and blood tests may not show her as a carrier. The child may still inherit the X-link mutation
Some children may have a vocabulary of up to a couple of hundred words; some may communicate through eye gaze, picture exchange systems or other communication systems. Most children are non verbal. However, the fact that they are non verbal doesn’t mean they cannot communicate so it’s important not to let that stop you from trying.
MCT8 Deficiency (AHDS) is hard to diagnose. The earliest observed abnormalities, at around 2-3 months of age, include floppy body and the inability to support their head. Typical thyroid tests that may indicate further research in this direction are high serum T3 and borderline low to low T4. Confirmation of the diagnosis requires genetic testing.
The affected gene is located in one of the mother’s X chromosomes. The mother (XX) will have one affected chromosome and one unaffected. In most cases, the unaffected chromosome takes up “the duties” of the affected one and that is why the mother is not a patient but a carrier. If the child is a boy (XY) it will need to take one X chromosome from the mother. If he takes the affected X, then he will be a patient. He has 50% changes of taking the affected chromosome. If it’s a girl, she also has 50% chances of taking the affected chromosome, however, in her case, she will be a carrier, like her mother.
In very rare instances this would be possible, only when the healthy X also has a mutation leaving both X’s to be ineffective and not work properly.
To this point there is no cure but medicine is progressing rapidly. There are therapies that may help improve the quality of life. There is also a medication that may decrease the blood toxicity (Triac) and in so doing reducing long term complication.
MCT8 is a protein that helps transport thyroid hormone into brain cells. Thyroid hormones are vital to the development of the brain. The MCT8 mutation affects each child differently due to different amounts of T3 getting into the cells to help the brain develop. Similar to a snowflake, no two children are exactly the same.
The thyroid hormone plays a critical role in brain development. T3 is a thyroid hormone that affects many processes in the body, including growth and development, metabolism, body temperature and heart rate. When the MCT8 protein functions normally, the T3 is allowed entry into the brain cells. When there is a mutation on the MCT8 protein, it creates an insufficient supply of T3 for the cells in the brain. Essentially each cell has a “door” to receive the T3. With the MCT8 mutation the “door” to the cell may not open to receive the T3 or the “door” may open slightly to receive the T3. Those individuals that have the “door” open slightly will be slightly less affected than those that do not have the “door”.
It is not known what is the minimal amount of thyroid hormone required for normal development. A reduction of 50% (like in the case of carrier mothers) does not create sever consequences. This has been shown experimentally in cultures of skin cells obtained from carrier mothers. The degree of impairment of hormone transport is dependent on the type of mutations.
In children with MCT8-AHDS the brain is unable to receive the proper amount of T3, therefore the brain is unable to develop critical areas required for speech, motor function and so on. This is why many of the boys can’t walk, talk, or sit unattended.
Due to the deprivation of T3 within the brain, the nerve cells are unable to send the proper signals to the rest of the body. This creates dystonic movements, seizures, hypotonia and other symptoms. This is often reflected on MRIs of the brain where the development of myelin (white matter) shows delay.
Depending on the mutation and severity of the syndrome, some children may communicate via basic vocabulary and some may be able to do sign language. Other options that work for some include eye gaze technology with communication software, picture communication systems (like PECS or PODD), Makaton and so on.
Depending on the mutation and severity of the syndrome, some children may walk with assistance/gait trainer.
Children may receive their nutrition in a variety of manners. Some children can eat orally (mainly with assistance), some do a combination of orally eating and have a feeding tube while others are feeding tube dependent.
Due to the child’s hypotonia many have swallowing and chewing difficulties which is why feeding tubes are very common. Swallowing and chewing difficulties may also lead to aspiration.
In children affected by MCT8 deficiency, the thyroid hormones may not reach the brain but they do reach all other tissues through additional transporters. Since there is no collaboration between the thyroid and the brain (which would have the role of adjusting the thyroid hormones production) the thyroid produces hormones in excess. All these extra hormones are transported to the other tissues by other transporters creating a state of excess. The thyroid hormone (T3) excess accounts, in part, for the increased metabolism and failure of weight gain. High blood T3 is the cause of inability to gain weight and malnutrition.
While its symptoms are not life threatening, their complications might be. Simple things like a not being able to turn their heads in their sleep may lead to suffocation. Gastric reflux is also very common and not threatening in normal conditions but for a child who can’t control swallowing may prove fatal. A simple infection that the care giver can’t be aware of because the child is not interacting with his environment may also be lethal. In conclusion, MCT8-AHDS does not have life threatening symptoms but the complications that it creates are.
Depending on the mutation and severity of the syndrome life expectancy varies with each child. Your child’s medical team will be able to answer this question best.
- Continued pneumonia’s
- Aspiration which can be fatal during sleep or awake periods
- Undetected infections (most commonly respiratory)
- Heart Failure
The most common indicator is that they cannot support their heads. This is the first milestone that a typical child reaches at the age of 3 months old. For children with MCT8-AHDS this is something that they will struggle with for the rest of their lives. In time they develop spasticity in the superior and inferior members while the body remains affected by hypotonia. .
- Lack of head control
- Central hypotonia combined in most cases with peripheral hypertonia
- Intellectual disability
- Inability to gain and maintain weight
- Increased heart rate – related to the high blood toxicity.
- Motor delay
- Low bone density – it is believed to be a symptom associated with high blood toxicity
- Epileptic seizures
- Sleep problems
- Problems swallowing/chewing food
Most start showing delay after the first few months of life.
The majority of boys do have sleep issues but not all. Contributing factors that can lead to sleep issues are reflux and dystonia.
Independently of paroxysmal dyskinesia, true seizures affect a small amount of children with MCT8 deficiency.
Only EEG can confirm seizures. As a parent you need to be the advocate for your child and push for what you feel he needs. It also may require multiple tests and times due to EEG testing not always being able to catch when your son has them. 48 EEG video monitoring is recommended.
Children who are involved in the family’s everyday life do better/have improvement. Be an advocate and involve them in regular family activities!
Even though some children have eyes problems (ex. strabismus) there has been no proven scientific connection between those and the syndrome.
Children with MCT8-AHDS tend to have problems maintaining a constant body temperature. This is an observational information based on the community's experience and we have no scientific explanation for it. It’s good to remember however that the thyroid hormone affects many processes in the body, including growth, development, metabolism, body temperature and heart rate.