Zellweger Syndrome Spectrum (PEX2-Related) (PEX2)
Zellweger syndrome spectrum (PEX2-related) is an autosomal recessive disease of peroxisome biogenesis. While it is found in many different ethnicities, it is more prevalent in individuals of Ashkenazi Jewish descent due to the presence of a founder mutation. It is comprised of three diseases that make up a continuum of severity, from the most severe, known as Zellweger syndrome, to neonatal adrenoleukodystrophy, to infantile Refsum disease, which is the mildest. Zellweger syndrome is characterized by demyelination of structures in the brain leading to leukodystrophy, resulting in seizures and vision loss. Clinical features also include dysmorphic features, hypotonia, cardiac problems, and dysfunction of the liver and kidneys. Death typically occurs in the first year of life. Neonatal adrenoleukodystrophy and infantile Refsum disease share many overlapping features. Onset of symptoms may be in infancy, or may be noticed later in childhood. Features include developmental delay and loss of vision and hearing; some children present with bleeding in the brain. The severity and course of the disease can vary between individuals; some may learn to walk and talk, and rarely, patients may survive until adulthood; others never walk or talk. Many patients do not survive childhood. Symptoms tend to progress in severity over the course of the patients life. Clear genotype-phenotype correlations of PEX2 variants have not been reported.
For information about carrier frequency and residual risk, please see the residual risk table.