Researchers have demonstrated the genetic basis of a group of rare, progressive, metabolic diseases that affect the brain, spinal cord and often the peripheral nerves called leukodystrophies.
Leukodystrophies primarily affect white matter and can develop at any age, leading to debilitating symptoms including memory and cognition problems; and impairments of the motor system and coordination. Leukodystrophies are often unfortunately fatal.
There are many causes of leukodystrophies, including infections, drugs and genetic abnormalities. The last group is usually the most difficult to diagnose and often patients with genetic causes of leukodystrophy spend many years seeking a diagnosis.
In a BRC supported study, published in Brain, a team from UCL/UCLH used the latest genetic techniques to characterise a large group of these patients, providing many with a diagnosis for the first time.
First author on the paper Dr David Lynch said: “We collected one of the biggest cohorts in the world of patients with adult onset leukodystrophy, allowing us to more accurately determine which genes more commonly cause leukodystrophy in adults. No previous study in this area was able to estimate the relative frequency of each gene and its contribution to this disease.”
Using the latest next generation sequencing technology, the team identified the genetic abnormality in 26 of these difficult to diagnose cases. They used this information to determine which genes most commonly cause leukodystrophy in adults. They also found that the focused sequencing approach, using a panel of genes, was just as effective as the more expensive whole exome sequencing which was later performed.
Dr Lynch said: “Our study provides a framework for neurologists to work within when they see a patient with one of these conditions. Most neurologists will only see an adult with leukodystrophy once every two years, so knowing which genes are more common and which approach is most likely to help make a diagnosis will improve care for patients. One of the most interesting genetic findings in our study was that autosomal recessive diseases, which we usually think of as causing disease in children, were relatively common in adults.”
This team anticipate the study will lead to improved diagnostic rates and better care for adults with these rare disorders; and hopefully shorten the time that it takes for a patient to receive a diagnosis after presenting with a leukodystrophy. It also provides some valuable insights into the phenotypes of some specific genes including AARS2, CTSA and CSF1R.
