PEX1-related Zellweger syndrome spectrum (ZSS) is an inherited disease that impairs the proper functioning of the body's peroxisomes, a cellular structure that normally breaks down fatty acids and other metabolic waste products.
As indicated by the word "spectrum," people with ZSS vary widely in the type and severity of their symptoms. The disease is generally grouped into three subtypes: Zellweger syndrome (the most severe), neonatal adrenoleukodystrophy (intermediate severity) and infantile Refsum disease (the mildest form). Each is described below. Individuals with ZSS usually show symptoms of the disease as newborns or as children.
While specific genetic mutations cannot fully predict which form of the disease a person will inherit, some genetic mutations are more closely associated with milder or more severe symptoms. Please consult a healthcare professional for more information.
Zellweger Syndrome (ZS)
ZS is the most severe form of ZSS. Infants with ZS usually die before their first birthday without reaching many mental or physical milestones.
Infants born with ZS have developmental delay leading to severe mental retardation. They often have seizures and typically have facial deformities such as a high forehead, abnormal ear lobes, a large "soft spot" on the top of their heads, and a small chin. In some, the lack of muscle tone is so severe that the infant cannot move and may not be able to suck or swallow. They often show poor feeding. Their livers are usually enlarged and their skin and the whites of their eyes may have a yellowish tinge (jaundice.) Some have bleeding in their digestive tract. Bone deformities are also common.
Neonatal Adrenoleukodystrophy (NALD) and Infantile Refsum Disease (IRD)
The symptoms of NALD and IRD are similar to that of ZS, but typically less severe, with NALD being more severe than IRD. Symptoms in these children often begin in late infancy or early childhood and may progress more slowly.
Infants and children with NALD or IRD may have developmental delays leading to mild to severe mental retardation. Hearing loss and vision impairment typically grow worse over time and may lead to blindness and/or deafness. Many people with the disease have liver problems and some have developed episodes of spontaneous bleeding, particularly around the brain. 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, though some do not.
ZSS affects 1 in 50,000 infants.
There is no cure for ZSS and there is no standard way to treat it. Physicians can address certain symptoms as they arise, such as prescribing medication for seizures. Children with milder forms of the disease may benefit from hearing aids, glasses, and/or surgery to remove cataracts. In those who reach school age, special education is likely necessary. Modifications to the child's diet may also be recommended.
In children with severe forms of the disease, the main goal of treatment is to protect the child from infections and breathing problems.
ZSS usually reduces a person's lifespan. One study showed that children with NALD or IRD who survive the first year of life have a 77% chance of reaching school age. These children will all have some degree of learning disabilities or mental retardation. Most people with NALD survive into childhood while those with IRD can live into their teens or 20s, and perhaps even longer.
The prognosis for an infant with ZS is poor. Most die within the first year of life without reaching any physical or mental milestones.
Explanations of an extensive number of genetic diseases written by the U.S. government's National Institutes of Health.
The Global Foundation for Peroxisomal Disorders is a resource for families who have received a diagnosis of Zellweger Syndrome, Neonatal Adrenoleukodystrophy (NALD), Infantile Refsum Disease (IRD), D-Bifunctional Protein Deficiency and Rhizomelic Chondrodysplasia Punctata (RCDP) through connections to medical professionals, scientific professionals and family support networks.
An agency of the U.S. government's National Institutes of Health, NINDS offers an easily understood description of Zellweger syndrome.