Adenine nucleotide translocator 1 deficiency associated with Sengers syndrome

• Published in: Annals of neurology Vol. 52; no. 1; pp. 95 - 99
• Main Authors: Jordens, Eric Z., Palmieri, Luigi, Huizing, Marjan, Van Den Heuvel, Lambert P., Sengers, Rob C. A., Dörner, Andrea, Ruitenbeek, Wim, Trijbels, Frans J., Valsson, Jullius, Sigfusson, Gunnlaugur, Palmieri, Ferdinando, Smeitink, Jan A. M.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.07.2002
• Subjects: Biological Transport - genetics; Female; Genetic Linkage - genetics; Humans; Male; Mitochondria, Heart - enzymology; Mitochondrial ADP, ATP Translocases - deficiency; Mitochondrial ADP, ATP Translocases - genetics; Mitochondrial Myopathies - enzymology; Mitochondrial Myopathies - genetics; Myocardium - enzymology; Pedigree; Syndrome
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.10214

Sengers syndrome is characterized by congenital cataracts, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis, but no abnormalities have been found with routine mitochondrial biochemical diagnostics (the determination of pyruvate oxidation rates and enzyme measurements). In immunoblot analysis, the protein content of the mitochondrial adenine nucleotide translocator 1 (ANT1) was found to be strongly reduced in the muscle tissues of two unrelated patients with Sengers syndrome. In addition, low residual adenine nucleotide translocator activity was detected upon the reconstitution of detergent‐solubilized mitochondrial extracts from the patients' skeletal or heart muscle into liposomes. Sequence analysis and linkage analysis showed that ANT1 was not the primary genetic cause of Sengers syndrome. We propose that transcriptional, translational, or posttranslational events are responsible for the ANT1 deficiency associated with the syndrome.