Since 2017, Genuity Science and CHI at Temple Street have been working together to identify rare and ultra-rare conditions in children with previously undiagnosed disorders. Mary Ann Cleary was referred to the rare disease programme in 2017 by her consultant Prof Mary King (consultant neurologist at CHI at Temple Street). Mary Ann was 8 years old and had suffered with a painful and debilitating condition called dystonia for several years. Over time she gradually lost the ability to speak, eat and walk. Routine genetic tests to look for large DNA abnormalities had not revealed any explanation for Mary Ann’s symptoms.

In 2017, her condition had rapidly deteriorated. She lost the ability to breathe on her own and she was admitted to intensive care and placed on life support. There was little hope that Mary Ann would survive.

To identify the genetic cause of Mary Ann’s condition, the research team at Genuity Science (formerly Genomics Medicine Ireland) sequenced her entire genetic code. Mary Ann’s doctors, alongside the Genuity Science research team, then reviewed all the variants in Mary Ann’s genetic sequence in order to identify potential variants that may be causing her condition. This genomic analysis resulted in the identification of a mutation in a gene called KMT2B. This gene had only recently been recognised to cause symptoms like Mary Ann’s and a treatment called deep brain stimulation had been identified, in adults, as a potential treatment. This treatment is not routinely used in children, however, due to the critical nature of Mary Ann’s condition her doctors decided to give deep brain stimulation a chance.

Following this treatment, there was an immediate and dramatic improvement in Mary Ann’s condition. Just weeks after the treatment, Mary Ann spoke for the first time in four years. She is now able to move around, speak, laugh and play.

The Genuity Science Rare Disease Programme continues to support CHI at Temple Street in using whole genome sequencing to search for the genetic cause of rare and ultra-rare conditions in children with undiagnosed disorders.