1. ¹University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London
2. ²Biochemistry, Endocrinology and Metabolic Unit, Institute of Child Health, University College London
3. ³Institute of Neurology, University College London
4. ⁴Clinical Chemistry Department, Birmingham Children's Hospital, Birmingham, United Kingdom
5. ⁵Department of Biochemistry, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands

Correspondence: Dr. Jan-Willem Taanman, University Department of Clinical Neurosciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: j.taanman@rfc.ucl.ac.uk

Received 29 January 2001.

Abstract

Conventional approaches to the diagnosis of mitochondrial respiratory chain diseases, using enzyme assays and histochemistry, are laborious and give limited information concerning the genetic basis of a deficiency. We have evaluated the diagnostic value of 12 monoclonal antibodies to subunits of the four respiratory chain enzyme complexes and F₁F_o-ATP synthase. Antibodies were used in immunological studies with skin fibroblast cultures derived from patients with diverse mitochondrial diseases, including patients in which the disease was caused by a nuclear genetic defect and patients known to harbor a heteroplasmic mutation in a mitochondrial tRNA gene. Immunoblotting experiments permitted the identification of specific enzyme assembly deficits and immunocytochemical studies provided clues regarding the genetic origin of the disease. The immunological findings were in agreement with the biochemical and genetic data of the patients. Our study demonstrates that characterization of the fibroblast cultures with the monoclonal antibodies provides a convenient technique to complement biochemical assays and histochemistry in the diagnosis of mitochondrial respiratory chain disorders.