[TS3-1C-1] How to Biochemically Approach Neuromuscular Disorders with Biochemical and Mass Spectrometric Procedures
Mass spectrometry including tandem mass spectrometry (TMS) and GC/MS are becoming popular in biochemical investigation of neuromuscular diseases. Organic acidemia (OA-emia) and fatty acid oxidation (FAO) defect, which often cause acute encephalopathy, myopathy, or even sudden infant death, are diagnosed by analysis of blood acylcarnitines (AC), and urinary organic acids (OA), using TMS and GC/MS, respectively.
OA-emias are clinically classified: 1) neonatal onset severe form; 2) infantile onset intermittent form like HMG-CoA lyase deficiency; 3) neuro-degenerative form like glutaric acidemia type1. FAO defects are roughly classified into 3 groups: 1) neonatal onset fatal form; 2) intermediate form with episodic attacks; and 3) myopathic form with skeletal muscle symptoms.
Metabolic profiles: specific AC findings suggest OA-emia or FAO defect, which can cause acute encephalopathy, myopathy, or even sudden death. Urinary OA analysis reveals OA-emia or transient suppress of metabolism (ex. dicarboxylic aciduria due to suppressed FAO).
In vitro probe assay: FAO capacity and defective sites is evaluated, using cultured fibroblasts and TMS. With this method, even acquired FAO defects like flu-encephalopathy, or Reye-like encephalopathy due to drug or toxin can be evaluated. Furthermore, it is used to develop new drugs for FAO defect.
Simple screening method for Leigh encephalopathy: Causes of Leigh syndrome is unknown in many cases. ECHS1 defect is a deficiency of the second step enzyme of short-chain FAO (crotonase), and was recently reported to be a possible cause of Leigh encephalopathy. Elevation of 2-methyl-2,3-diOH-butyrate which suggests ECHS1 defect is a simple screening marker for Leigh encephalopathy.
OA-emias are clinically classified: 1) neonatal onset severe form; 2) infantile onset intermittent form like HMG-CoA lyase deficiency; 3) neuro-degenerative form like glutaric acidemia type1. FAO defects are roughly classified into 3 groups: 1) neonatal onset fatal form; 2) intermediate form with episodic attacks; and 3) myopathic form with skeletal muscle symptoms.
Metabolic profiles: specific AC findings suggest OA-emia or FAO defect, which can cause acute encephalopathy, myopathy, or even sudden death. Urinary OA analysis reveals OA-emia or transient suppress of metabolism (ex. dicarboxylic aciduria due to suppressed FAO).
In vitro probe assay: FAO capacity and defective sites is evaluated, using cultured fibroblasts and TMS. With this method, even acquired FAO defects like flu-encephalopathy, or Reye-like encephalopathy due to drug or toxin can be evaluated. Furthermore, it is used to develop new drugs for FAO defect.
Simple screening method for Leigh encephalopathy: Causes of Leigh syndrome is unknown in many cases. ECHS1 defect is a deficiency of the second step enzyme of short-chain FAO (crotonase), and was recently reported to be a possible cause of Leigh encephalopathy. Elevation of 2-methyl-2,3-diOH-butyrate which suggests ECHS1 defect is a simple screening marker for Leigh encephalopathy.