Chapter 11 - Peroxisomal disorders: Clinical and biochemical laboratory aspects

Abstract

Peroxisomes are ubiquitous dynamic and interactive subcellular cytoplasmic organelles with diverse biochemical functions including the metabolism of very long chain fatty acids (VLCFAs), biosynthesis of plasmalogens, cholesterol, and bile acids, as well as redox homeostasis, which require a complex set of peroxisome membrane and matrix proteins that allow proper biogenesis and function. Clinically, defective peroxisomal structure or function results in a group of recognizable neurometabolic syndromes of varying severity including peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies with classical Zellweger syndrome and X-linked adrenoleukodystrophy, respectively representing the prototypes for these disorders. In addition to the distinctive clinical signs and symptoms associated with many of these disorders, biochemical abnormalities including elevated levels of plasma VLCFA (>C22:0), phytanic acid, pristanic acid, low erythrocyte or fibroblast plasmalogens, complementation analysis, single enzyme measurement, brain magnetic resonance imaging, direct mutation analysis using Sanger as well as next generation sequencing are used to confirm such diagnoses. More recently, newborn screening for adrenoleukodystrophy using mass spectrometry analysis of (C26:0) lyso-phosphatidylcholine (C26:0-LPC) in dry blood spots had been demonstrated, which may allow early diagnosis and treatment. In addition to supportive therapies, other therapeutic options include plasmapheresis, dietary restriction of VLCFA and phytanic acid as well as hematopoietic stem cell therapy. Gene therapy is still investigational and potentially promising.