Peroxisome biogenesis disorder

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 :

• 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 .

Generally, the Zellweger spectrum disorders present in infant- or childhood and are characterized by crainofacial dysmorphism, neurological abnormalities, jaundice and developmental delay . 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 .

Rhizomelic chondrodysplasia punctata type 1 presents with shortening of the proximal humerus and femur, with punctate calcification of the epiphyseal cartilage . Dysplasia of the epi- and metaphysis, early-onset cataracts, seizures and intellectual disability are also common .

Pathology

The PBDs are caused by mutations in the pexin (PEX) genes, which encode peroxins that allow for appropriate peroxisome biogenesis .