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Ann Clin Biochem. 2003 Jan;40(Pt 1):3-8.

Some practical aspects of providing a diagnostic service for respiratory chain defects.

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Nijmegen Centre for Mitochondrial Disorders, Department of Pediatrics, University Medical Centre Nijmegen, Geert Grooteplein 10, PO Box 9101, 6500 HB Nijmegen, The Netherlands.


The oxidative phosphorylation system (OXPHOS) is organized into five multi-protein complexes, comprising four complexes (I-IV) of the respiratory chain and ATP synthase (complex V). OXPHOS has a vital role in cellular energy metabolism and ATP production. Enzyme analysis of individual OXPHOS complexes in a skeletal muscle biopsy remains the mainstay of the diagnostic process for patients suspected of mitochondrial cytopathy. Practical guidelines are presented to provide optimal conditions for performance of laboratory investigations and a reliable diagnosis. A fresh muscle biopsy is preferable to a frozen muscle sample because the overall capacity of the OXPHOS system can be measured in a fresh biopsy. In about 25% of patients referred for muscle biopsy to our centre, reduced substrate oxidation rates and ATP+creatine phosphate production rates were found without any defect in complexes I-V and the pyruvate dehydrogenase complex. Investigation of frozen muscle biopsy alone may lead to false-negative diagnoses in many patients. In some patients, it is necessary to investigate fibroblasts for prospective diagnostic purposes. An exact diagnosis of respiratory chain defects is a prerequisite for rational therapy and genetic counselling. Provided guidelines for specimen collection are followed, there are now reliable methods for identifying respiratory chain defects.

[Indexed for MEDLINE]

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