A clinical and genetic study based at UCL Institute of Neurology and the Institute of Child Health, recently published in Brain, has used next generation sequencing to identify riboflavin transporter gene defects as the defective pathway in a severe form of childhood motor neuron disease. Children with these defects significantly respond to high dose riboflavin.
First described by Charles Brown in 1894, children and young adults develop speech and swallowing problems, face and limb weakness and breathing problems, many also have hearing problems. Prior to this finding, treatment was restricted to supportive care and many died before the age of 20 years.
The genes identified using the latest
techniques developed at UCL Institute of Neurology, both encode riboflavin
transporters are called SLC52A3 and SLC52A2. So far nearly 30 families have
been identified.
Treating children with high-dose riboflavin leads to
significant improvement in their condition; many gain weight, come off
ventilation, can move and use their hands and have objective improvement in
nerve function, although the use of this treatment is still in the early
stages.
This is the first treatable cause of a type of motor neuron disease,
thus highlighting the importance and translatable potential of next generation
sequencing in neurological disorders.
At UCL Institute of Neurology the research was led by Professor Henry Houlden (h.houlden@ucl.ac.uk) and colleagues at the MRC Centre for Neuromuscular Diseases
Further information:
Foley et al. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. Available online 19 November 2013. doi: 10.1093/brain/awt315
Details of the genetic test and
riboflavin treatment protocol can be obtained by contacting Professor Houlden.