What Is Refsum Disease? What Are Its Symptoms? How Is It Treated?

What Is Refsum Disease? What Are Its Symptoms? How Is It Treated?

In this article, we will examine the details regarding this topic. Refsum diseases are rare genetic disorders that lead to problems with the breakdown of fats. Infantile Refsum disease is more severe and generally affects life expectancy. People with adult Refsum disease can usually manage their symptoms by limiting their consumption of certain foods.

What Is Refsum Disease?

Refsum disease actually consists of two distinct genetic conditions: infantile Refsum disease and adult Refsum disease. Both are part of a group of disorders known as peroxisomal disorders, in which genetic changes (mutations) impair the breakdown of specific types of fat. People with this condition lack the enzymes that help break down a type of fat called phytanic acid, leading to its accumulation in the body.

Difference Between Adult and Infantile Refsum Disease

Both adult and infantile Refsum disease can cause vision loss and phytanic acid accumulation. However, these two conditions stem from two different gene mutations present before birth:

• Infantile Refsum Disease: Part of a group of disorders called Zellweger spectrum disorders. These cause symptoms in infants and young children such as floppy muscle tone, poor feeding, seizures, developmental delays, and liver disease. It is more severe than adult Refsum disease. While life expectancy varies, it is ultimately fatal.
• Adult Refsum Disease: Appears in late childhood or later. It primarily causes vision loss, loss of smell, weakness or numbness in the hands and feet, and hearing impairment. It does not affect the brain like infantile Refsum disease, so individuals typically do not experience seizures or developmental delays. However, serious heart problems can develop later in life.

Prevalence and Symptoms

How Common Is Refsum Disease?

Refsum disease is extremely rare. Infantile Refsum disease occurs in approximately 1 in 100,000 people, whereas adult Refsum disease occurs in about 1 in 1,000,000 people.

Symptoms of Refsum Disease

Symptoms vary depending on the age at which they begin to appear.

• Infantile Refsum Disease Symptoms:
• Markedly decreased muscle tone at birth and feeding difficulties.
• Seizures or abnormalities in kidneys, liver, and long bones.
• Infants with severe forms often pass away within the first year of life.
• Older children may display: Developmental disabilities, poor growth, and vision/hearing problems.
• Adult Refsum Disease Symptoms:
• Loss of night vision caused by retinitis pigmentosa (almost always the first symptom, starting in adolescence, youth, or adulthood). Retinitis pigmentosa can progress to peripheral vision loss or complete blindness.
• Loss of sense of smell (anosmia).
• Numbness or tingling in the hands or feet.
• Hearing loss and balance issues.
• Scaly or rough skin patches (ichthyosis).
• Cloudy vision (cataracts).
• Serious heart issues such as arrhythmias or heart failure.

Complications and Causes

Complications of Refsum Disease

• Infantile: Severe and debilitating. Children experience feeding issues, seizures, and sensory impairments. Life expectancy is shortened due to respiratory complications.
• Adult: Vision, strength, sensory perception, and balance progressively worsen over time. Physical stressors (severe illness or surgery) can cause phytanic acid levels to spike, leading to irregular heart rhythms or severe weakness. Untreated arrhythmias can be life-threatening.

Causes of Refsum Disease

Refsum disease is caused by a gene mutation present from birth, inherited from one or both biological parents.

• Infantile: Caused by mutations in over a dozen genes. The most common are PEX1 (60%), PEX6 (15%), PEX12 (7.6%), and PEX26 (4.2%).
• Adult: About 9 out of 10 individuals have a mutation in the PHYH gene. Most of the remaining individuals have a mutation in the PEX7 gene.

Diagnosis and Treatment

Diagnosis

Doctors use different tests depending on the patient's age, followed by genetic testing to search for specific gene mutations.

• Infantile: The most common diagnostic tests measure very long-chain fatty acids, phytanic acid, and pristanic acid.
• Adult: Blood tests are initially used to check phytanic acid levels.

Treatment

• Infantile: Management focuses on present symptoms. Interventions include tube feeding, cataract removal surgery, corrective glasses, hearing aids, vitamin supplementation, anti-seizure medications, and therapy/early intervention services for developmental delays.
• Adult: Requires limiting foods high in phytanic acid, including:
• Beef and lamb.
• Dairy products.
• Fatty fish (e.g., cod, tuna, or haddock).
• Plasmapheresis: Some individuals require this treatment to filter out excess phytanic acid from the blood.

• Questions to Ask Your Doctor

  • What are the early signs of Refsum disease?
  • Which tests are used to diagnose Refsum disease?
  • What are the treatment options for Refsum disease?
  • Do I need to undergo genetic testing for Refsum disease?
  • What is the probability of passing Refsum disease to a child?

  Learning that you or your child has a rare genetic disease can be frightening, but receiving a diagnosis is the first step in understanding what is happening. Medical teams will work together to create a customized treatment plan based on specific symptoms and disease progression. Connecting with a support group can be especially helpful for parents of children with Refsum disease. While everyone’s experience differs, sharing experiences with other parents and caregivers provides valuable support.