Refsum Disease

What is Refsum disease?

Refsum disease is actually two distinct genetic disorders: infantile Refsum disease and adult Refsum disease. They’re both part of a group of diseases known as peroxisomal disorders, in which genetic changes (mutations) lead to problems breaking down certain types of fat. If you have this condition, you don’t have enzymes that help break down a type of fat called phytanic acid. As a result, phytanic acid builds up in your body.

What is the difference between adult Refsum disease and infantile Refsum disease?

Both adult and infantile Refsum disease can cause vision loss and phytanic acid buildup. But these two conditions result from two different gene changes (mutations) that develop before you’re born:

• Infantile Refsum disease is part of a group of disorders called Zellweger spectrum disorders. They cause symptoms in babies and young children, including floppy muscle tone, poor feeding, seizures, developmental delays and liver disease. Infantile Refsum disease is more severe than adult Refsum. Life expectancy for babies with this disease can vary, but the condition is eventually fatal.
• Adult Refsum disease occurs in late childhood or after. It primarily causes vision loss, loss of smell, weakness or numbness of your hands and feet, and hearing impairment. It doesn’t affect your brain like infantile Refsum, so people don’t usually have seizures or developmental delays. But they can develop severe heart problems later in life.

How common is Refsum disease?

Refsum disease is extremely rare. Infantile Refusm happens in about 1 in 100,000 people, while adult Refsum happens in about 1 in 1 million people.

What are the symptoms of Refsum disease?

The symptoms of Refsum disease vary depending on how old you are when you start having symptoms.

Infantile Refsum

If your child has infantile Refsum disease, they may be born very floppy and feed poorly. Their symptoms will depend on how severe their disease is. They may have seizures or abnormalities of their:

• Kidneys.
• Liver.
• Bones (long bones).

Infants with severe disease often die within the first year of life.

Older children can have:

• Developmental disabilities.
• Poor growth.
• Visual and hearing issues.

Adult Refsum

The first symptom of adult Refsum disease is almost always a loss of night vision caused by retinitis pigmentosa. Your child may notice night blindness during their adolescence or teenage years. Or they may not develop symptoms until they’re adults. As they get older, retinitis pigmentosa may progress to loss of peripheral vision or blindness.

Other Refsum disease symptoms include:

• Loss of smell (anosmia).
• Numbness or tingling in their hands or feet.
• Hearing loss.
• Balance issues.
• Scaly or rough skin patches (ichthyosis).
• Cloudy vision (cataracts).
• Severe heart problems, like arrhythmia or heart failure.

What are the complications of Refsum disease?

Infantile Refsum is severe and disabling. Children have problems with feeding, seizures, vision and hearing. They have shortened lifespans from respiratory complications.

In adult Refsum, your vision will get worse over time. Weakness, sensory deficits and balance issues also gradually worsen over time. Physical stressors — like severe illness or surgery — can cause extremely high phytanic acid levels, leading to an irregular heartbeat or extreme weakness. Without treatment, arrhythmias can be life-threatening.

What causes Refsum disease?

Refsum disease occurs because of a gene mutation (change) that you’re born with. You inherit these gene mutations from one or both of your biological parents.

There are over a dozen genes that can cause infantile Refsum. The most common are PEX1 (60%), PEX6 (15%), PEX12 (7.6%) and PEX26 (4.2%).

Adult Refsum also occurs because of an inherited gene mutation that’s present at birth. About 9 in 10 people with adult Refsum disease have a mutation in the PHYH gene. Most others with the condition have a PEX7 gene mutation.

How is Refsum disease diagnosed?

Healthcare providers use different tests to arrive at a diagnosis for Refsum disease depending on your age. Then, they might order genetic tests to look for the gene mutations that cause Refsum disease.

For infantile Refsum, the most common diagnostic tests are very long-chain fatty acids, phytanic acid and pristanic acid. For adult Refsum, your healthcare provider may initially use a blood test to check your phytanic acid levels.

How is Refsum disease treated?

For infantile Refsum disease, your child’s healthcare provider will base their treatment on their symptoms. Interventions may include tube feeding, cataract removal, glasses, hearing aids, vitamins, anti-seizure medications and therapies/early intervention services for developmental delays.

For adult Refsum disease, treatment includes limiting your intake of foods that increase your phytanic acid levels, including:

• Beef and lamb.
• Dairy products.
• Fatty fish, like cod, tuna or haddock.

Some people may also need a treatment called plasmapheresis to control phytanic acid buildup. In plasmapheresis, a healthcare provider draws your blood, filters extra phytanic acid out, then reinfuses it back into your body.

Do I need heart treatment for Refsum disease?

In the rare case that you develop an irregular heartbeat in adult Refsum disease, you may need treatment to control your heart rhythm, including:

• Medications, like beta-blockers, calcium channel blockers or anticoagulants, to regulate your heart rate or reduce stroke risk.
• Cardioversion, a controlled electric shock to restore a typical heart rhythm.
• Implantable cardioverter defibrillator, a device placed under your skin that monitors and regulates your heartbeats.
• Catheter ablation, a minimally invasive procedure that intentionally damages diseased heart tissue to disrupt an irregular heart rhythm.

How can I reduce my risk of Refsum disease?

Refsum disease is a genetic disorder, so there’s no way to prevent it.

If you have Refsum disease or think you could be a carrier, you may consider genetic testing. Genetic testing identifies the gene mutation that causes Refsum disease. A genetic counselor can help you understand test results, including your chances of passing any genetic conditions to your children.

What can I expect if I have Refsum disease?

Children with infantile Refsum generally have severe developmental disabilities and require many medical interventions. Unfortunately, despite vigilant care, people with the condition have shortened lifespans due to the severity and nature of this disorder.

In adult Refsum, most people successfully manage their symptoms by limiting their intake of foods that are high in phytanic acid. With treatment, symptoms like dry skin, numbness or tingling often disappear. You may deal with vision or hearing loss long term. In some people, a lost sense of smell never returns.

What questions should I ask my doctor?

If you have Refsum disease or think you could, you may want to ask your healthcare provider:

• What are the early signs of Refsum disease?
• What tests diagnose Refsum disease?
• What are the treatment options for Refsum disease?
• Should I get genetic testing for Refsum disease?
• What are the chances that I’ll pass Refsum disease to my child?

A note from Cleveland Clinic

It can be scary to hear that you or your child have a rare genetic disorder. But getting a diagnosis is the first step to understanding what’s going on. Your healthcare providers will work together to develop a treatment plan that’s tailored to your symptoms and outlook (or those of your child.) Especially if you have a child with Refsum disease, it might help to connect with a support group. Although everyone is different, it may help to talk about your experience with other parents and caregivers.