When is the flu more than just a passing infection? The answer to that all depends on your genetic inheritance, according to researchers at the Laboratory of Human Genetics of Infectious Diseases. This joint French-American lab found certain DNA mutations may cause a subtle dysfunction in the immune system. And for children with these alleles, an everyday flu may be life-threatening.

The flu: fever, headaches, fatigue, muscle pain. These symptoms of infection are caused by a virus, which subtly changes every season. While vaccination may improve your chances of not getting infected, once you become sick, not much can be done. In most cases, we stay in bed, treat the symptoms, and recover within a week.

Some people are vulnerable to developing very severe forms of the flu, which may include potentially fatal respiratory distress. Unsurprisingly, chronic lung disease and other very specific medical conditions increase a person’s risk for developing a severe flu, but in some cases, people — especially children — die without explanation. There’s just one more added peculiarity: Patients with acquired immune-deficiencies, which usually increase susceptibility to infection, are somehow not vulnerable to severe influenza.

Adding up these facts, Dr. Jean-Laurent Cassanova, Dr. Laurent Abel, both of University Paris Descartes/Inserm, and their lab colleagues speculated that severe influenza in healthy children might be the result of genetic errors.

To test their hypothesis, the research group sequenced the genome of a child who had contracted Influenza A (H1N1) at the age of 2-and-a half. She had become so sick she required admission to a pediatric intensive care unit. At the time, she showed no sign of other illnesses that might explain her susceptibility. To learn more, the researchers sequenced her parents’ genomes after completing the girl’s analysis, and compared all the results.

The little girl had inherited from both her parents a mutated allele of the gene which codes for interferon regulatory factor (IRF7), the researchers discovered. Normally, this gene increases the production of interferons, which help the immune system fight off any pathogens, including viruses like the flu. While her parents each carry just one mutation, the little girl carries a mutation of both alleles; though one flaw is apparently harmless, a double mutation is another story. As a result of the double mutation, her gene is inactivated and the girl’s body does not produce interferons as it should and so her immune system cannot fight a relatively harmless virus like the flu.

A series of experiments on the girl's blood cells plus an analysis of lung cells generated from her stem cells provided the researchers with further proof that her double mutation explains her life-threatening encounter with the flu. While they propose further research, the research team believes a type of pharmaceutical drugs, recombinant interferons, could help combat severe forms of influenza in all children with a similar genetic mutation.

Source: Ciancanelli MJ, Huang SXL, Luthra P, et al. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science. 2015.