peroxisome biogenesis disorder type 1

What Is Peroxisome Biogenesis Disorder Type 1?

Peroxisome biogenesis disorder type 1 (also known as PEX1-related Zellweger syndrome spectrum, ZSS) is an inherited disease that affects the functioning of the body's peroxisomes, a structure in the body's cells that normally breaks down fatty acids and other metabolic waste products. As indicated by the word "spectrum," individuals with ZSS vary widely in the type and severity of their symptoms. The disease is generally grouped into three subtypes: Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (a form of intermediate severity), and infantile Refsum disease (the mildest form). ZSS results from mutations in the PEX1 gene. Because mutations cannot always predict which form of the disease a person will have, families should consult a healthcare professional for more information about each form described below.

Zellweger Syndrome (ZS)

ZS is the most severe form of ZSS. Infants with ZS usually die before their first birthday without reaching any developmental milestones. Infants with ZS generally have very low muscle tone, severe developmental delay, and seizures. In some, the lack of muscle tone is so severe that the infant cannot move and may be unable to suck or swallow. Most infants with ZS have some degree of feeding and breathing difficulties. In addition, skeletal changes and liver problems are common, and episodes of spontaneous bleeding (including in the brain) are possible. Infants with ZS also tend to have characteristic facial features, including a high forehead, abnormal earlobes, a large "soft spot" on the top of their heads, and a small chin.

Neonatal Adrenoleukodystrophy (NALD) and Infantile Refsum Disease (IRD)

The symptoms of NALD and IRD are less severe than those of ZS. Symptoms in children with these conditions often begin in late infancy or early childhood and may progress more slowly than those in ZS. Infants and children with NALD or IRD typically have developmental delays and mild to severe intellectual disability. Some children with the disease learn to walk, while others lack the muscle tone needed for such movement. Similarly, many children with the disease learn to talk, while others do not. Hearing loss and vision impairment are present and typically worsen over time, potentially leading to deafness and/or blindness, respectively. Many children with NALD or IRD have liver problems and some have developed episodes of spontaneous bleeding, particularly around the brain.

How Common Is Peroxisome Biogenesis Disorder Type 1?

The estimated prevalence of peroxisomal biogenesis disorders is 1 in 50,000, with almost 70% of cases being due to mutations in the PEX1 gene.

How Is Peroxisome Biogenesis Disorder Type 1 Treated?

There is no cure for ZSS, and there is no standard way to treat it. In children with severe forms of the disease, the main goal of treatment is to protect the child from infections and breathing problems. Physicians can also address certain symptoms as they arise, such as prescribing medication for seizures. Children with milder forms of the disease may benefit from hearing aids and glasses, as well as physical, occupational, and speech therapy. In those who reach school age, special education is likely necessary. Modifications to the child's diet may also be recommended.

What Is the Prognosis for a Person with Peroxisome Biogenesis Disorder Type 1?

Individuals with ZSS have a shortened lifespan that varies depending on the severity of the disease. The prognosis for an infant with ZS is poor. Most die within the first year of life without achieving any developmental milestones. Most children with NALD survive into childhood, while those with IRD can live into their teens or 20s, and perhaps even longer. All individuals with NALD or IRD will all have some degree of cognitive impairment.