Refsum Disease: What It Is, Symptoms, and How It Is Treated

Have you ever heard of Refsum disease? This rare condition is likely new to many people because it is a very uncommon genetic disorder passed down through families. Learning about rare conditions helps you stay informed about your health and body.

Refsum disease affects how your body processes specific dietary fats. Let us explore what this condition means, how it affects adults and children, and what medical options exist today.

What Is Refsum Disease?

Simply put, Refsum disease includes two different genetic conditions known as infantile Refsum disease and adult Refsum disease. Both types belong to a broader group of conditions called peroxisomal disorders.

When you have this condition, genetic changes, or mutations, prevent your body from properly breaking down certain fats. If you have Refsum disease, your body lacks the specific enzymes needed to break down phytanic acid. As a result, phytanic acid builds up inside your body, much like unwanted clutter piling up in your home.

Difference Between Adult and Infantile Refsum

Both types of Refsum disease involve vision loss and a buildup of phytanic acid in your body. However, these conditions develop due to changes in two different genes before birth.

• Infantile Refsum Disease: This condition belongs to the Zellweger spectrum disorders and affects infants and young children. Signs include floppy muscle tone, poor feeding, seizures, developmental delays, and liver disease. Infantile Refsum is much more severe than the adult form. While life expectancy varies, this condition can eventually become life-threatening.
• Adult Refsum Disease: This type usually appears in late childhood or later in life. Main features include vision loss, loss of sense of smell, numbness or weakness in your hands and feet, and hearing loss. Unlike infantile Refsum, it does not directly affect the brain, so seizures and developmental delays do not occur. However, severe heart problems can develop later in life.

How Common Is Refsum Disease?

Refsum disease is an extremely rare condition. Infantile Refsum occurs in about one out of every one hundred thousand people. Adult Refsum is even rarer, affecting about one out of every one million people. These numbers show just how uncommon this medical condition is.

Symptoms of Refsum Disease

The symptoms of Refsum disease vary depending on the age when the condition first appears.

Infantile Refsum Symptoms

If your child has infantile Refsum disease, their muscles may feel very floppy at birth, almost lacking strength. Feeding can also be very difficult for them. Their symptoms depend on the severity of the condition and may include seizures as well as abnormalities in organs such as your kidneys, liver, and long bones.

Babies with severe forms of this condition may not survive past their first year of life. Older children with this condition may experience developmental disabilities, poor growth, and vision or hearing challenges.

Adult Refsum Symptoms

The earliest symptom of adult Refsum disease is almost always trouble seeing at night, known as retinitis pigmentosa. Your teenager might notice this night blindness around age thirteen or fourteen, or they might show no symptoms at all until adulthood. As you grow older, this condition can narrow your side vision and eventually lead to total blindness.

Other symptoms of adult Refsum disease include:

• Loss of your sense of smell, known as anosmia.
• Numbness, tingling, or burning feelings in your hands and feet.
• Reduced hearing ability.
• Balance issues and trouble staying steady.
• Dry, scaly patches on your skin, known as ichthyosis.
• Blurry vision or clouding of your eye lenses, similar to cataracts.
• Severe heart problems, such as irregular heartbeats or heart failure.

Complications of Refsum Disease

Infantile Refsum is a very serious and disabling condition. Children face major challenges with eating, seizures, vision, and hearing. Respiratory complications also tend to shorten their lifespan.

In adult Refsum, your vision slowly worsens over time. Weakness, reduced sensation, and balance issues also increase gradually. During periods of physical stress, such as a major illness or surgery, your phytanic acid levels can rise sharply. This surge can trigger dangerous heart rhythm problems or severe weakness. Without treatment, these heart rhythm issues can threaten your life.

Causes of Refsum Disease

Refsum disease happens because of a gene mutation present from birth. You inherit these changed genes from your mother, your father, or both parents.

More than twelve different genes can cause infantile Refsum. The most common ones include PEX1, accounting for about sixty percent of cases, PEX6 at fifteen percent, PEX12 at nearly eight percent, and PEX26 at four percent.

Adult Refsum also stems from an inherited gene mutation present from birth. About nine out of ten people with adult Refsum have a mutation in the PHYH gene. This most others have a mutation in the PEX7 gene.

Think of this like a small factory inside your body where a vital machine breaks down. When those genetic machines fail to work properly, health problems arise.

How Doctors Diagnose Refsum Disease

Doctors use various tests depending on your age to diagnose Refsum disease. Genetic tests can then look for the specific gene mutations responsible for the condition.

• For Infantile Refsum: Common tests measure very long-chain fatty acids, phytanic acid, and pristanic acid levels in your blood.
• For Adult Refsum: Your doctor will likely start by taking a blood sample to check your phytanic acid levels.

Treatment Options for Refsum Disease

Treatments for Infantile Refsum

If your child has infantile Refsum disease, their doctor will tailor treatments to manage specific symptoms. Supportive care options include:

• Tube feeding to ensure proper nutrition.
• Cataract removal surgery to improve vision.
• Eyeglasses for better sight.
• Hearing aids for hearing support.
• Vitamin supplements.
• Anti-seizure medicines.
• Therapies and early intervention services for developmental delays.

Treatments for Adult Refsum

When treating adult Refsum disease, you need to limit foods that raise your body's phytanic acid levels. Foods to avoid or limit include:

• Beef and lamb meats.
• Dairy products such as milk, cheese, and butter.
• Oily fish species like cod, tuna, or haddock.

Some people also need a procedure called plasmapheresis to control phytanic acid buildup. During plasmapheresis, a medical specialist removes some of your blood, filters out the excess phytanic acid, and returns the cleaned blood to your body. Although this treatment is complex, it helps many patients greatly.

Do You Need Treatment for Heart Conditions Caused by Refsum Disease?

In adult Refsum disease, sudden irregular heartbeats require prompt medical attention. Treatments to manage your heart rhythm include:

• Medicines: Beta-blockers, calcium channel blockers, or blood thinners help control your heart rate and lower stroke risks.
• Cardioversion: A controlled electrical shock helps restore a normal heart rhythm.
• Implantable Cardioverter Defibrillator (ICD): A small device placed under your skin monitors your heartbeat and regulates it automatically.
• Catheter Ablation: A minimally invasive procedure that uses targeted energy to block abnormal heart tissue signals.

What to Expect with Refsum Disease

Children with infantile Refsum usually experience severe developmental challenges and require extensive medical support. Tragically, due to the severe nature of this condition, many affected children have shortened lifespans despite best care efforts.

Many people with adult Refsum successfully manage their symptoms by restricting dietary phytanic acid. With proper treatment, issues like dry skin and numbness often improve. However, you may live with long-term vision or hearing challenges, and lost senses of smell may not return.

How to Lower Risks Associated with Refsum Disease

Because Refsum disease is a genetic condition, you cannot prevent it from occurring. However, if you have Refsum disease or suspect you carry the gene, genetic testing offers valuable insights.

Genetic tests can identify the specific gene mutations responsible for Refsum disease. A genetic counselor can help you understand your test results and explain the likelihood of passing this condition to your children.

Questions to Ask Your Doctor

If you or someone in your family has Refsum disease or shows related symptoms, consider asking your doctor these questions:

• What are the earliest signs of Refsum disease to watch for?
• Which diagnostic tests should we perform?
• What treatment options best match our situation?
• Should I consider genetic testing for my family?
• What is the likelihood that my children could inherit Refsum disease?

Discovering that you or your child has a rare genetic condition can feel frightening. However, obtaining an accurate diagnosis is the first essential step toward understanding what lies ahead.