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

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 complex...

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Bibliographic Details
Published in:Annals of clinical biochemistry 2003-01, Vol.40 (1), p.3-8
Main Authors: JANSSEN, A. J. M, SMEITINK, J. A. M, VAN DEN HEUVEL, L. P
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Biological and medical sciences
Biopsy
Errors of metabolism
Fibroblasts - metabolism
Humans
Medical sciences
Metabolic diseases
Miscellaneous hereditary metabolic disorders
Mitochondrial Diseases - diagnosis
Mitochondrial Myopathies - diagnosis
Models, Biological
Muscle, Skeletal - pathology
Oxidative Phosphorylation
Oxygen - metabolism
Prenatal Diagnosis
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Summary: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.
ISSN:0004-5632
1758-1001
DOI:10.1258/000456303321016114