Manganese toxicity: tackling a disabling condition and a possible link with ADHD
A researcher based at University of College London’s Institute of Child Health is investigating the role of the metal manganese in the body, and looking for ways to protect children from its damaging effects. The new study is being funded by children’s charity Action Medical Research.
Manganese, though essential to health, causes brain damage and can contribute to movement disorders (Parkinson’s disease and dystonia) in children if levels in the body rise too high. Those who are vulnerable include premature babies fed intravenously and children with a rare metabolic disorder.
Almost every baby who is born prematurely before 28 weeks of pregnancy has to be fed intravenously and some babies have developed manganese toxicity as a result. Recently, it has even been suggested that high levels of manganese in soya-based infant feeds might be implicated in the development of attention deficit hyperactivity disorder (ADHD).
Dr Karin Tuschl has been awarded a prestigious Research Training Fellowship* worth £200,000 to help her investigations to explain how high levels of manganese can lead to health problems.
Dr Tuschl recently discovered that a rare genetic disorder, for which there is no cure, is linked to errors in manganese metabolism.1 “Children with this rare disorder typically experience difficulties walking and have problems with fine motor movements, such as writing,” says Dr Tuschl. Many become wheelchair users in their teens and, sadly, several have died early due to liver cirrhosis.
Current treatment for this rare illness is inadequate. “Children have to attend hospital for around one week every month to have intravenous infusions that take five to seven days,” explains Dr Tuschl.
“My ultimate aim is to find a treatment that alleviates physical disability, so children don’t lose their ability to walk for example, protects the brain and spares children from losing their lives to liver damage,” she says.
She is developing a new laboratory model of manganese toxicity specifically for her work. This will be used to test the potential of several different drugs in the lab in her quest to find better treatments for children who have abnormally high levels of manganese in their bodies. She also aims to offer genetic testing to any children who are suspected of having the rare genetic disorder so that they can get an accurate diagnosis.
“I feel very privileged to have the opportunity to work on this exciting project,” says Dr Tuschl. “It has real potential to help to improve quality of life for children and their families.”
Dr Caroline Johnston, Research Evaluation Manager with Action Medical Research, said: “The Research Training Fellowship scheme is the cornerstone of Action Medical Research’s commitment to develop the research expertise and skills of the future.”
“By giving the brightest and best doctors and researchers the chance to train in research techniques early in their career, we are helping to ensure that the first-rate medical research work that Action Medical Research has become synonymous with will continue for a long time to come.”
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Case study: patient 'M' (the name Mary has been given to the patient in this story)
One of nine siblings, Mary was a healthy girl before painful and disabling symptoms started when she was 11 years old. Her legs became stiff and she would suffer from painful spasms. She developed difficulties walking and was not able to run anymore. She also had stiff hands that made it difficult for her to pick up and hold things like cutlery, toothbrush and pens – so she became unable to write or draw.
At that time, doctors did not know what the cause was or how to treat it. The fact that her older brother had had the same symptoms suggested it may be a genetic disorder. He died of complications of the disorder when he was just 18, so Mary’s parents were understandably keen for a cure to be found.
Mary’s symptoms were found to be caused by hypermanganesemia, where levels of manganese in the body are allowed to rise too high. The metal manganese, though essential to health, causes brain damage if the body has too much of it. The children’s charity Action Medical Research is funding Dr Karin Tuschl, of University College London’s Institute of Child Health, in her investigations into the role of manganese and ways to protect children from its damaging effects.
As well as this genetic disorder, those who are also vulnerable include premature babies who are fed intravenously and children with liver disease. High levels of manganese in soya-based infant feeds have also been implicated in the development of attention deficit hyperactivity disorder (ADHD).
Because of her physical disability caused by hypermanganesemia, Mary could not take part in normal activities that others her age would do, like running, dancing and ball games. At times she needed to use a wheelchair and could only leave the house with assistance and became dependent on her family to complete simple tasks. Despite these difficulties, Mary continued to go to school and made good progress.
A happy and smiley girl, Mary coped incredibly well with her illness. She came to the Great Ormond Street Hospital in 2002. “Every year when we saw her in clinic she remained positive despite her movement difficulties and this encouraged doctors to continue looking for a cause of her illness,” says Dr Tuschl.
Mary was the first patient with hypermanganesemia to be treated with intravenous infusions of a medication that would help her body to get rid of the toxic levels of manganese in her brain and liver. Happily for Mary and her family it was successful.
Now 22, living overseas, Mary’s disability is improved – she is able to write and walk much better. Her associated liver disorder has also not progressed. The infusions of medication she needs are now given in her local hospital, which each month means a five-night stay for Mary. She continues to come to London every year for follow up with Dr Tuschl and the team.
Thanks to funding from children’s charity Action Medical Research, Dr Karin Tuschl is now trying to find a new treatment that Mary, and others like her, will be able to take at home to allow a relatively undisrupted life away from hospital.
NOTES TO EDITORS:
*Research Training Fellowships: each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research.
1. Tuschl K et al. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet 2012; 90:457-66.
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Action Medical Research - the leading UK-wide medical research charity dedicated to helping babies and children - is celebrating 60 years of vital research in 2012. We’ve been funding medical breakthroughs since we began in 1952 and have spent more than £100 million on research that has helped save thousands of children’s lives and changed many more. Today, we continue to find and fund the very best medical research to help stop the suffering of babies and children caused by disease and disability. We want to make a difference in:
- tackling premature birth and treating sick and vulnerable babies
- helping children affected by disability, disabling conditions and infections
- targeting rare diseases that together severely affect many forgotten children.
But there is still so much more to do. Make 2012 a special year and help fund more life-changing research for some of the UK’s sickest babies and children.