PEX7-related disorders

What are PEX7-related disorders?

PEX7-related disorders are a group of conditions that impact multiple body systems and have a wide range of severity. They are caused by harmful genetic changes (variants) in the PEX7 gene. PEX7-related disorders affect the function of a part of the cell called the peroxisomes. The peroxisomes are responsible for both building and breaking down a number of different substances in the body.

PEX7-related disorders consist of a classic or mild form of rhizomelic chondrodysplasia punctata type 1 (RCDP1) and adult Refsum disease (ARD). The symptoms depend on the type of harmful change an individual has.

Rhizomelic Chondrodysplasia Punctata Type 1 (Classic Form)

Children with the classic form of RCDP1 experience symptoms that begin at birth or within the first few months of life. They grow very slowly, leaving them much smaller than expected for their age. They often have short upper arm and thigh bones. X-rays of the cartilage show areas with increased calcium (punctate calcifications). Individuals have severe intellectual disabilities and are not expected to develop skills beyond the level of a normally developing six-month-old infant. Other symptoms can include stiff joints (contractures), cataracts, seizures, lung infections, breathing problems, hearing loss, distinct facial features, spinal cord issues, and heart defects.

Rhizomelic Chondrodysplasia Punctata Type 1 (Mild Form)

In the mild form or RCDP1, intellectual disability and growth deficiency are less severe. Children with this form are typically delayed in their development but eventually learn to walk and talk. Cataracts, stiff joints, and increased calcium in the cartilage are common symptoms. Seizures, behavior problems, and heart defects may also occur.

Adult Refsum Disease

Individuals with adult Refsum disease have a specific type of eye problem, called retinitis pigmentosa, which causes progressive vision loss. Most individuals also experience a loss of their sense of smell (anosmia). Nerve damage affecting both the nerves involved in movement and sensation (polyneuropathy) is common. This can lead to symptoms such as muscle weakness, numbness, and abnormal reflexes. Other common features include balance issues (ataxia), dry scaly skin (ichthyosis), shortened bones in the hands and feet, hearing loss, and heart abnormalities. Although it is called "adult" Refsum disease, features can begin anywhere from infancy until after age 50. Most people notice their first symptoms in their teenage years.

How common are PEX7-related disorders?

There are several genes that are known to cause rhizomelic chondrodysplasia punctata (RCDP), which occurs in less than 1 in 100,000 individuals. PEX7 is the most common cause of RCDP. Similarly, there are several genes that are known to cause ARD, which has an incidence of 1 in 1,000,000 births. Less than 10% of ARD is caused by harmful changes in PEX7.

How are PEX7-related disorders treated?

There is no cure for the underlying cause of PEX7-related disorders. Treatment for the condition is directed at managing the specific symptoms an individual has. Individuals with RCDP1 may benefit from physical therapy for stiff joints, surgery to remove cataracts or correct spinal cord issues, and seizure medications. It is also important to monitor for breathing problems and respiratory infections. In some cases, a feeding tube may be helpful.

A diet that is low in phytanic acid is typically recommended for those with ARD and may also be beneficial in the milder form of RCDP1. Other treatments for ARD may include medications to treat dry skin or heart issues. In severe cases, a special machine may be used to decrease phytanic acid levels by removing blood from the body and filtering it before sending it back.

What is the prognosis for an individual with a PEX7-related disorders?

Prognosis depends on the specific type of PEX7-related disorder that a person has. The prognosis for a child with the classic form of RCDP1 is poor. Many children with this form die in the first or second year of life, and only half survive beyond the age of 10. Breathing problems are often the cause of death. Those with milder forms of RCDP1 typically live longer, with the majority surviving into adulthood.

The prognosis of individuals with ARD is variable, and a normal lifespan is possible. A diet that is low in phytanic acid can slow the progression of symptoms. Heart abnormalities are a common cause of early death in this condition.