Biochemical Diagnosis of OXPHOS Disorders

Abstract

In this chapter the biochemical diagnosis of OXPHOS disorders is presented. The laboratory investigations in suspected patients are started with the examination of body fluids. The most important metabolite to be measured is lactate, that is frequendy found to be elevated in blood, urine and cerebrospinal fluid of patients with OXPHOS disorders. The next step in the diagnostic procedure consists of the examination of tissues. The biochemical diagnostic investigations are preferably performed in muscle tissue because in most patients the defect is expressed in muscle. Biopsy material is preferred above autopsy material. Biochemical examination of a fresh muscle sample is to be preferred because mitochondria are intact in fresh muscle thus allowing measurement of the overall oxidative capacity of the mitochondria. In a frozen muscle sample only enzyme activities of the OXPHOS complexes can be measured. In the latter case patients with a disturbance in the oxidative phosphorylation not localized in one of the OXPHOS complexes remain undiagnosed. Practical guidelines for the biochemical examinations of muscle are provided. In certain circumstances it is necessary to examine also fibroblasts. This is an absolute prerequisite in case prenatal diagnosis is requested. The interpre-tation of the biochemical investigations is discussed with special emphasis on the observed residual enzyme activities.