Overview of Refsum Disease

Refsum disease is an inherited genetic disease that falls into a group of genetic disorders called leukodystrophies, which cause problems with fat metabolism. It’s a recessive genetic condition, meaning you usually only develop it when you receive an associated mutation from both parents.

More than 90% of cases of Refsum disease are thought to result from a mutation in the PHYHgene. Most other cases are caused by a mutation in PEX7. These mutations cause the atypical function of peroxisomes, structures inside your cells that allow your body to break down the fatty acid phytanic acid.

Phytanic acid comes from your diet in sources like:

• meat from mammals, such as:
  • sheep
  • cow
  • goat
• dairy products like butter or cheese
• baked goods containing animal fats
• oily fish
• some nuts and related plants like:
  • almonds
  • coconuts
  • peanuts

Refsum disease isn’t known to affect any racial group more than others and occurs in people of all sexes at about the same rate.

People with classic Refsum disease usually don’t develop symptoms until they’re between the ages of 10 and 20 years. Sometimes, symptoms don’t develop until the age of 50.

People with the infantile version develop symptoms shortly after birth.

The first symptom is usually loss of night vision (retinitis pigmentosa). Other signs and symptoms can include:

• small pupils
• rapid and involuntary eye movement (nystagmus)
• cataracts
• loss of taste and loss of smell
• progressive deafness,
• numbness and weakness in hands and feet
• unsteady gait
• rough, scaly patches of skin
• weakness
• shortened bones in your fingers and toes

In a 2023 study, researchers found that 85.7% of people with Refsum disease had vision impairment and 64.3% had dry skin at an average of 12 years after their diagnosis.

Excessively high levels of phytanic acid in the tissues of people with Refsum disease can damage nerves and organs. It can cause complications, such as:

• cardiomyopathy, a disease of the heart muscle
• arrhythmia, an atypical heart rate
• progressive loss of vision
• progressive hearing loss
• ataxia, trouble with muscle coordination
• diabetes
• high blood pressure
• muscular atrophy
• kidney atrophy

Refsum disease is rare, and its symptoms can have many other potential causes. It’s important to see a doctor if you or your child develop potential symptoms, such as:

• trouble with movement
• changes to your eyesight
• changes to your hearing
• weakness or numbness in your hands and feet
• sudden trouble balancing

The results of a blood test can suggest Refsum disease if you have elevated phytanic acid levels in your sample. The diagnosis can be confirmed with a genetic test to look for an associated mutation in your gene PHYHor PEX7.

The classic form of the disease can sometimes be diagnosed between the ages of 2 and 7 years but often gets delayed until early childhood. The infantile version is often diagnosed in early adulthood.

The primary treatment for the classic and infantile forms of Refsum disease is minimizing your intake of foods high in phytanic acid. Ideally, daily phytanic acid consumption should be less than 10 milligrams per day.

Other ways to improve the course of the disease include:

• consuming a high calorie diet to avoid the breakdown of stored phytanic acid
• avoiding ibuprofen, amiodarone, and other medications that increase thyroid hormone levels
• very closely monitoring phytanic acid levels during pregnancy
• receiving plasmapheresis, where plasma is removed from your blood

The survival rate for the infantile version of Refsum disease is usually 5–13 years, but some children survive into adulthood. People with the classic form of the disease often live into their 30s or 40s.

The outlook is often poor for people who don’t receive treatment or don’t follow their treatment plan. Arrhythmias are a frequent cause of death.

Strict diet management is important. Hearing and visual loss aren’t reversible, but other symptoms like muscle weakness and skin symptoms may resolve when you lower your daily intake of phytanic acid.

Refsum disease is caused by genes inherited from your parents and isn’t preventable. You can reduce the course of classic Refsum disease by following your doctor’s instructions and strictly reducing phytanic acid levels.

Here are some frequently asked questions people have about Refsum disease.

What is the name of the enzyme deficiency in Refsum disease?

People with Refsum disease have a deficiency in an enzyme called phytanoyl-CoA hydroxylase.

What is the triad of Refsum disease?

The triad of features, or condition markers, of Refsum disease include:

• retinitis pigmentosa and loss of vision
• weakness and numbness in your limbs
• poorly coordinated movements

Is Refsum disease fatal?

Refsum disease often causes premature death. Most people with the adult form of the disease live into their 30s or 40s. People with the infantile version often pass away before their teens.

Refsum disease is a genetic condition characterized by the buildup of a type of fat in your tissues called phytanic acid. The buildup of this fat can cause symptoms like vision loss or weakness and numbness in your limbs.

Avoiding foods high in phytanic acid may help improve the course of your disease. Meat, dairy, and fatty fish are the main sources of this fat.