Peroxisome biogenesis disorders (PBD) are illnesses that affects the formation of peroxisomes, a part of the body’s cells responsible for breaking down waste products.
These diseases are divided into three subtypes: Zellweger syndrome (the most severe), neonatal adrenoleukodystrophy (intermediate severity), and infantile refsum disease (the mildest form). People with PBD typically display symptoms from birth or childhood, but some may not show signs until later.
Zellweger syndrome (ZS) is the most severe type of PBD. Infants with ZS often don’t live past their first birthday and may not reach important mental or physical milestones. They experience developmental delays, leading to severe intellectual disability. Seizures are common, and facial differences like a high forehead, abnormal ear lobes, a large “soft spot” on the head, and a small chin are typical. Some infants have weak muscles, making it difficult to move, suck, or swallow. Poor feeding, enlarged livers, yellowish skin, and bleeding in the digestive tract are common. Abnormal bone shapes may also occur.
Neonatal adrenoleukodystrophy (NALD) and infantile refsum disease (IRD) are less severe than ZS, with IRD being the mildest. Signs usually appear in late infancy or early childhood and progress more slowly. Children may experience developmental delays with mild to severe intellectual disability. Hearing and vision problems may worsen over time, leading to blindness and/or deafness. Liver issues and spontaneous bleeding, especially around the brain, can occur. Some children with the disease learn to walk and talk, while others may struggle with muscle tone.
There’s no cure for PBD, and treatment varies based on the severity. For severe cases, the main goal is to protect the child from infections and breathing issues. Medication can be prescribed for seizures, and those with milder forms may benefit from hearing aids, glasses, or cataract surgery. Special education and dietary modifications may be recommended for those reaching school age.
This group of conditions is caused by pathogenic (disease-causing) variants in at least 12 genes and the test we offer covers 5 including PEX1 (type 1), PEX12 (type 3), PEX6 (type 4), PEX2 (type 5), and PEX10 (type 6). All exhibit autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 227 chance to be a carrier for type 5.
Other names for this condition are cerebrohepatorenal syndrome and Zellweger syndrome spectrum.
Resources:
Global Foundation for Peroxisomal Disorders
Medline Plus – Zellweger syndrome
National Institute of Neurological Disorders and Stroke – Infantile Refsum Disease
Revised November 2023
