Organelle pathology in metabolic neuromuscular disease: an overview

Abstract

The spectrum of metabolic neuromuscular disorders is wide. Most inherited metabolic diseases are related to enzyme defects within lysosomes but recent advances emphasize abnormalities of mitochondria, peroxisomes and intermediate filaments. In this overview, organelle pathology is described in the context of both the clinical manifestations and the biochemical and/or molecular aspects of the disease. Among the many clinical presentations of mitochondrial disorders three emerge as distinctive entities: mitochondrial encephalopathy with lactic acidosis and stroke-like symptoms, mitochondrial encephalopathy with ragged-red fibers, and Kearns-Sayre syndrome. Peroxisomal disorders are associated with numerous biochemical defects, the most frequent of which are Zellweger's syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease. Disorders of cytoskeletal proteins are associated with distinctive pathological accumulation of intermediate filaments but are without confirmed evidence of a biochemical defect. Understanding the role that organelle pathology plays in the pathogenesis of cellular disturbance or demise is essential to the elucidation of the pathogenesis of metabolic disorders.