Tabby's story: TANGO2 deficiency disorder

When Tabby was born, her mum Hannah felt as though something wasn’t right. Tabby couldn’t breastfeed and had lost a lot of weight. However, this was put down to trauma from birth and it was decided that a ‘watch and wait’ approach was best.

That changed when Tabby was about a year old and had a very bad choking episode, during which Hannah’s neighbours had to resuscitate Tabby. At that moment, a health visitor agreed that there was an underlying issue that needed to be investigated. Tabby was also experiencing episodes where she lost muscle control. Hannah remembers: “There were times when she went completely floppy, but others when she was as stiff as a board.”

Tabby underwent her first batch of genetic testing and a paediatrician diagnosed her with 22q11 deletion, also known as DiGeorge syndrome. This is a genetic condition that can cause numerous health issues, including heart defects and learning difficulties.

However, many more tests followed in the years afterwards as Tabby was displaying symptoms that were outside her 22q11 deletion diagnosis, such as her episodes of losing muscle control, and Hannah wanted to know why.

Getting a diagnosis

Hannah first read about the 100,000 Genomes Project in 2016 on the SWAN (syndromes without a name) Facebook page. After researching it herself, she decided to enrol Tabby. She says: “I had decided that this was going to be the last attempt trying to understand more about Tabby’s difficulties. It wasn’t fair on Tabby to keep doing all these tests. She was starting to become very traumatised by hospitals and it didn’t seem fair to keep going.”

Hannah was not expecting to get any results back. However, a few years later she received a call asking her to come into the hospital. It was there that she was told that the testing had found that Tabby had a condition known as TANGO2 deficiency disorder.

Hannah says: “My first reaction was saying ‘oh my god’ and crying, although I did also think that it’s good we know what we’re dealing with.

“We didn’t really know anything about the condition at first since it’s very rare, just that Tabby had it. It was in the appointments afterwards it became clear that it was very serious, more than I had expected.

“I found it really frustrating that TANGO2 was such a rare condition and there wasn’t much information out there about it. As far as I’m aware there are only 12 children in the UK who have it. I had many questions that there just aren’t answers to.”

Living with TANGO2 deficiency disorder

Because of the diagnosis, Hannah now knows that when Tabby gets sick she needs to go straight to hospital for a drip and heart monitoring, as there is the risk of a heart attack.

For Hannah, that is one positive that has come with a diagnosis: “Getting a diagnosis has meant Tabby can have the monitoring and treatment that she needs. We’re quite fortunate in that regard that there were no heart problems during any of Tabby’s crises before the diagnosis.”

Tabby’s movement is also very variable – some days she needs a wheelchair while others she can walk. She has learning difficulties as well as gastrointestinal, eye and speech issues. Hannah says: “Since Tabby has two genetic conditions, it’s quite hard to differentiate and determine what causes what.

“I reached out to the TANGO2 Research Foundation after the diagnosis. They’ve been really helpful and it’s been good to be able to speak with other families who have experienced the same things that you have.”

How whole genome sequencing can help those with TANGO2 deficiency disorder

For Hannah, one difficult aspect was the wait to find out what was causing Tabby’s various difficulties. Whole genome sequencing and genetic testing led to the diagnosis of TANGO2 and 22q11 deletion respectively.

Hannah reflects: “The quicker a diagnosis can come, the better. The ultimate end goal would obviously be a cure that can fix the problem, either for Tabby or for others, and that comes through research that whole genome sequencing and diagnoses enable to better understand the gene and the condition.”