Paediatrics: Peroxisomal disorders

Peroxisomal disorders

Peroxisomes are ubiquitous cellular organelles that function to rid the cell of toxic material. They contain a number of oxidative enzymes and have an important role in the metabolism of fatty acid molecules. Peroxisomal disorders result in abnormalities of lipid metabolism.

Classification of peroxisomal disorders

Disorders of peroxisome development

•   Zellweger syndrome

•   Neonatal adrenoleucodystrophy

•   Infantile Refsum disease

•   Hyperpipecolic acidaemia

Defects in peroxisome function

•   Rhizomelic chondrodysplasia punctata

•   DHAP acyltransferase deficiency

•   Acyl-CoA oxidase deficiency

•   Bifunctional enzyme deficiency

•   X-linked adrenoleucodystrophy*

•   Primary hyperoxaluria –Type 1*

•   Acatalasaemia*

•   Disorders that do not have ‘severe peroxisome phenotype’.

Most peroxisomal disorders are associated with ‘severe peroxisome phenotype’ and share many common features including:

•   severe neurodevelopmental delay;

•   hypotonia/weakness;

•   seizure;

•   hepatic dysfunction;

•   impaired hearing or vision;

•   Sudanophilic leucodystrophy.

Diagnosis is made with liver biopsy and electron microscopy morphologi-cal studies. Blood analysis demonstrates characteristic biochemical abnor-malities (particularly very-long chained fatty acid, phytanic acid, and bile salt metabolites).

Zellweger syndrome

The classic peroxisomal disorder, due to defect in peroxisome biogenesis. ‘Severe peroxisome phenotype’; leads to death within few months of birth.

Infantile Refsum disease

Severe peroxisome phenotype with retinal degeneration, decreased plas-ma cholesterol, increased plasma phytanate. Survival to early childhood.