What is SAVI?

FORGE’s current focus is on the rare genetic disease SAVI syndrome. Find out more about this condition below.

Explaining SAVI

SAVI is a rare disease caused by a change in a gene called STING-1. The word “STING” is short for “Stimulator of Interferon Genes.”

SAVI stands for ‘STING-Associated Vasculopathy with Onset in Infancy’.

The STING1 gene helps turn on the interferon response. In people with SAVI, this response is excessive – the body produces too much interferon, even when it’s not needed. As the name suggests, SAVI usually appears in infancy.

What causes SAVI?

This diagram represents the STING1 gene which has 7200 bases (A, T, G and C). A single base substitution at a number of different positions in the STING1 gene can lead to SAVI for example, there is a single substitution error at position 463, where there should be a G (Guanine), there is instead an A (Adenine).

This tiny change, just one wrong letter, leads to SAVI.

There are around 20,000 genes in the human genome, with 3 billion base pairs (6 billion bases). Errors in DNA are common. Most errors have no effect, or are quietly repaired. But sometimes, even one wrong bases in the right (or wrong) place can lead to serious disease.

Credit: www.biopixelprints.com

The high ongoing levels of interferon cause a lot of inflammation, especially in the lungs and around blood vessels. This inflammation causes scarring, damaging the lungs to the extent that the children need additional oxygen. Ultimately, SAVI leads to respiratory failure. The inflammation can be so bad that those with the condition can experience ulcers and eventually lose their fingers, toes, ears, and nose.

Left untreated, SAVI has a five-year mortality rate or 30%. Our current focus is on SAVI.

Frequently asked questions

Are monogenic interferonopathies passed from parent to child?

Monogenic interferonopathies are genetic, which means they are caused by a change in a gene. This gene change can sometimes be passed down from a parent, but not always.

There are a few ways that the faulty gene can arise:

Inherited from a parent: In some cases, a child gets the changed gene from one or both parents, even if the parents don’t have any symptoms themselves.
New (spontaneous) mutation: Sometimes, the gene change happens by chance in the child, and neither parent has it. This is called a de novo (new) mutation.

Genetic testing can help find out where the change came from and whether other family members might be affected or carriers.

How many people have a monogenic interferonopathy?

Monogenic interferonopathies are very rare conditions. Only a small number of children around the world are known to have one.

These conditions may affect as few as 1 in 100,000 to 1 in a million children. Some types, like Aicardi–Goutières syndrome (AGS), have only a few hundred known cases worldwide. SAVI syndrome may be even rarer although because symptoms can be confused with other illnesses, some cases probably go undiagnosed, so the actual number may be higher.

Because these conditions are so rare — and their symptoms can look like other diseases — some children may not get the right diagnosis right away. That means the real number of affected children could be a little higher than we currently know.

Even though very few people have these conditions, the research being done to understand and treat them can help with other, more common diseases too — like lupus, severe COVID-19, and certain kinds of arthritis in children.

What is a monogenic interferonopathy?

A monogenic interferonopathy is a rare condition that is present from birth and typically presents in infancy. It happens because of a change in one important gene (that’s what “monogenic” means).

This gene change causes the immune system, the body’s defence system, to make too much of a protein called interferon. Interferon is supposed to help protect us from viruses and infections, but in this condition, the body makes too much of it which can lead to problems like inflammation in the brain, skin, lungs, or other parts of the body. Symptoms often begin in early childhood. Doctors and scientists are working to find better treatments, including medicines that calm the immune system or block the faulty gene.

Funded research vacancies

We do not currently have funded research vacancies. We anticipate opportunities will become available in the future. We welcome expressions of interest and will update this page accordingly