Seven people with a mysterious disorder that triggers a fever every few weeks have finally been given a diagnosis. A genetic analysis has revealed that all of them have a previously unknown disorder now called CRIA syndrome.
The individuals, who were aged between 10 and 82 when they were first assessed, belong to three families in the US. All reported having had a fever every two to four weeks since they were babies, during which their body temperature can climb as high as 41°C.
“You can imagine that having a fever and swollen lymph nodes every two weeks is not a good life,” says Najoua Lalaoui at Walter and Eliza Hall Institute of Medical Research in Australia. Some also experience other symptoms, including nausea, diarrhoea and mouth ulcers.
To find out what might be causing these symptoms, Lalaoui and her colleagues looked at the individuals’ genes. Specifically, the team studied the exomes, the regions of DNA that code for proteins.
The team found that all seven individuals have a mutation in a gene called RIPK1. The disorder caused by this mutation has never been described before, says Lalaoui.
In another experiment, Lalaoui and her colleagues genetically engineered mice to carry the same mutation, which also had symptoms of the disorder. When these mice were given fragments of bacteria, their immune systems appeared to mount an exaggerated response, and the animals showed more signs of inflammation and cell death.
The new finding may lead to more effective treatments for the seven affected individuals, as well as others given the same diagnosis. A separate research team in China has identified two further families with the same mutation and similar symptoms.
Currently, some of the affected individuals in the US are taking expensive drugs that target substances involved in inflammation in the body. But they don’t work for all those with the mutation, and they can cost more than $ 30,000 a year. Drugs that specifically target RIPK1 may be a better option, says Lalaoui. Such drugs are currently being developed, although none has yet been approved, she says.
Journal Reference: Nature, 10.1038/s41586-019-1828-5; Nature, 10.1038/s41586-019-1830-y
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