Zellweger Syndrome

Zellweger Spectrum Disorders, also known as Peroxisome Biogenesis Disorders, are a group of inherited disorders caused by the failure of the body to produce peroxisomes that are responsible for breaking down toxic substances and synthesizing lipids (fatty acids, oils, and waxes). PBD is comprised of three disorders that have considerable overlap of features. These include Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (NALD, intermediate form), and Infantile Refsum disease (IRD, the least severe form). Symptoms of these disorders include abnormal facial features, such as a high forehead, underdeveloped eyebrow ridges, and wide-set eyes, as well as an enlarged liver. Neurological abnormalities such as intellectual disability and seizures are also common. Infants with Zellweger syndrome lack muscle tone, sometimes to the point of being unable to move, and may not be able to suck or swallow. Some babies will be born with glaucoma, retinal degeneration, and impaired hearing. Jaundice and gastrointestinal bleeding also may occur. Infants with Zellweger Syndrome typically die in the first year of life. Those with NALD or IRD generally have symptoms beginning later in life and live longer. It is not possible to reliably predict which disorder any specific mutation may cause. Currently there is no cure for PBD, but medical surveillance and care may help to improve some symptoms and overall condition of life. PBD is caused by mutations in several genes, including the PEX1 gene and the PEX2 gene.

Zellweger Spectrum Disorders are inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for Zellweger Spectrum Disorders. However, the risk to have a child affected with these disorders is increased. Testing of reproductive partners is recommended for carriers of Zellweger Spectrum Disorders.

These disorders occur worldwide, with estimated to occurrence of 1 in 50,000 newborns in general population, although variation is observed among populations. In Japan, the estimated occurrence is only 1 in 500,000 newborns.

Genetics Home Reference: Zellweger spectrum (http://ghr.nlm.nih.gov/)

OMIM [PBD1A: 214100] (http://www.ncbi.nlm.nih.gov/omim)
OMIM [PBD1B: 601539] (http://www.ncbi.nlm.nih.gov/omim)
Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing