Peroxisopathies

Peroxisopathies are inherited disorders caused by defects in peroxisomes, the cellular organelles that perform lipid metabolism and detoxification. They are generally categorized into peroxisomal biogenesis disorders, where cells fail to assemble functional peroxisomes, and single enzyme deficiencies, in which peroxisomes are present but lack a specific function.

Peroxisomal biogenesis disorders include the Zellweger spectrum, ranging from severe neonatal forms to milder childhood forms. Common features are hypotonia, craniofacial dysmorphism, hepatomegaly, and early brain involvement. Other PBDs include infantile Refsum disease and Heimler syndrome. Single enzyme deficiencies include X-linked adrenoleukodystrophy (ABCD1), D-bifunctional protein deficiency, and phytanoyl-CoA hydroxylase deficiency (Refsum disease).

Biochemical hallmarks are elevated plasma very long-chain fatty acids and reduced plasmalogens, with variable changes in bile acid intermediates. Diagnosis combines biochemical testing with genetic analysis of PEX genes (PBDs) or ABCD1 (ALD), and occasionally functional peroxisomal assays in fibroblasts.

Treatment is largely supportive. In X-ALD, early hematopoietic stem cell transplantation may slow progression in cerebral disease; adrenal insufficiency is treated with hormone replacement. Dietary strategies to limit VLCFA intake and, in some cases, Lorenzo’s oil have been used; prognosis depends on the specific disorder and severity.