Peroxisome biogenesis disorders (PBDs) are autosomal recessive, inborn errors of peroxisomes, a eukaryotic cell organelle critical to the breakdown of very long chain fatty acids via beta-oxidation.
Clinical presentation
There are two main groups 1:
-
Zellweger spectrum disorder (ZSD)
- Zellweger syndrome (ZS)
- X-linked adrenoleukodystrophy (ALD)
- infantile Refsum disease (IRD)
- rhizomelic chondrodysplasia punctata type 1 (RCDP) - a type of chondrodysplasia punctata.
The Zellweger spectrum disorders overlap in clinical presentation, with Zellweger syndrome having the most severe symptomatology, X-linked adrenoleukodystrophy a milder presentation, and infantile Refsum disease milder, still 1,2.
Generally, the Zellweger spectrum disorders present in infant- or childhood and are characterized by crainofacial dysmorphism, neurological abnormalities, jaundice and developmental delay 1. More recently, the nomenclature has changed to "severe", "intermediate" and "mild" forms of Zellweger spectrum disorders, in place of Zellweger syndrome, X-linked adrenoleukodystrophy and infantile Refsum disease 1.
Rhizomelic chondrodysplasia punctata type 1 presents with shortening of the proximal humerus and femur, with punctate calcification of the epiphyseal cartilage 3. Dysplasia of the epi- and metaphysis, early-onset cataracts, seizures and intellectual disability are also common 3.
Pathology
The PBDs are caused by mutations in the pexin (PEX) genes, which encode peroxins that allow for appropriate peroxisome biogenesis 2.