SMA and liver damage
Last updated July 15, 2025, by Marisa Wexler, MS
Fact-checked by Jose Lopes, PhD
Spinal muscular atrophy (SMA) is a genetic disorder that’s marked by muscle weakness and wasting. An emerging body of research suggests that people with SMA are at increased risk of certain forms of liver damage.
In particular, data suggest that people with SMA may be at high risk of developing fatty liver disease. There are also some therapies used to treat SMA that can cause liver damage as a side effect.
Liver damage can in some cases be life-threatening, so prevention and management of liver complications in SMA is vital.
Potential causes of liver damage in SMA
There are two main types of SMA liver complications. They are:
- fatty liver disease
- liver damage due to treatment side effects.
Fatty liver disease
Fatty liver disease is a term that broadly refers to disorders wherein excess amounts of fat build up in the liver. In SMA, the term usually refers specifically to metabolic dysfunction-associated steatotic liver disease (MASLD), which is marked by the buildup of liver fat in people who have underlying metabolic conditions such as diabetes, high blood pressure, or high levels of blood fat. The excessive buildup of liver fat, known medically as steatosis, can lead to inflammation and scarring in the liver, which can set the stage for liver failure or liver cancer.
SMA is caused primarily by mutations in the SMN1 gene, which provides instructions to make a protein called survival motor neuron, or SMN. In SMA, levels of SMN protein are abnormally low, which leads motor neurons, the nerve cells that control movement, to sicken and die, driving most disease symptoms.
Metabolic complications in SMA are common. This is likely due in part to the fact that SMA causes muscle weakness, meaning many patients are unable to be physically active in the way typically developing people are. People with SMA also may require special diets or get nutrition via tube feeding, which may also contribute to metabolic abnormalities.
The absence of SMN protein in SMA may directly contribute to metabolic abnormalities, data suggest. In particular, some research indicates there’s a close association between SMN protein deficiency and liver function, meaning liver steatosis in SMA may be due in part to the fact that liver cells lack SMN protein in the disease.
Treatment side effects
Some SMA treatments can cause liver damage as a side effect. Most notably, the SMA gene therapy Zolgensma (onasemnogene abeparvovec-xioi) has been reported to cause liver damage.
Zolgensma is a one-time treatment that delivers a healthy version of the SMN1 gene to cells. The therapy is approved in the U.S. to treat people with SMA younger than 2. Zolgensma is also approved in dozens of other countries, though specific indications may vary.
In the U.S., prescribing information for Zolgensma contains a boxed warning noting it can cause liver dysfunction and that cases of fatal acute liver failure have been reported. People with preexisting liver issues may be at higher risk. Because of this risk, it’s recommended that liver function be checked in all patients before Zolgensma treatment and regularly for at least three months after it is given.
Zolgensma uses a modified virus to deliver the SMN1 gene to cells. This viral vector is designed to not cause infection, but the body’s immune system cannot tell the difference between the vector and a disease-causing virus. As such, when Zolgensma is administered by infusion into the bloodstream, the immune system may mount an inflammatory defense in the same way it would normally respond to an infection. It’s thought that the immune system’s inflammatory reaction to the viral vector is the main reason that liver damage can occur with Zolgensma.
Because of this, patients with SMA treated with Zolgensma are usually also given anti-inflammatory corticosteroids to help reduce the risk of liver damage.
Symptoms and early warning signs
Liver damage may not be obvious in SMA. In particular, symptoms of fatty liver disease often don’t become apparent until the disease has already progressed to the point that it is starting to cause liver damage. Medication-related liver damage is usually more acute and, as such, may be more readily apparent.
Symptoms and signs of liver damage include:
- nausea
- weakness and fatigue
- loss of appetite and unexplained weight loss
- itchy skin
- jaundice (a yellow coloring of the skin and whites of the eyes)
- swelling and/or pain in the abdomen and/or limbs
- bleeding in the digestive tract.
Diagnosis and monitoring
The main way to check liver function in SMA involves blood tests. When the liver is damaged, certain liver enzymes get released into the blood. As such, blood tests to look for elevated liver enzyme are a primary method to diagnose and monitor liver damage.
Liver enzyme elevations may be detectable even before an SMA patient has developed any overt symptoms of liver disease, so these blood tests are usually the main method for hepatic monitoring during SMA gene therapy.
Other tests may also be used to assess liver health in SMA. A liver ultrasound, which uses high-frequency sound waves to visualize the liver, can detect steatosis and may be used to diagnose and monitor the severity of fatty liver disease.
Managing and preventing liver issues
Common steps to help prevent liver disease in SMA include:
- the use of anti-inflammatory medications and close monitoring during gene therapy treatment
- eating a well-balanced diet that doesn’t have too much fat or sugar
- staying as physically active as possible.
It is generally easier to prevent and manage liver damage when the damage is detected early. As such, over the long term SMA patients may have regular checkups and liver function tests to look for any early signs of damage.
If liver disease does develop, managing it will depend on its underlying cause.
In people with fatty liver disease, treatment may involve dietary changes that seek to reduce the total amount of fat in the liver and reduce portion sizes. In acute liver injury caused as a side effect of therapy, managing it may involve anti-inflammatory medications or referral to a liver specialist.
SMA News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
