|22 April 2012
Location: Naarden, The Netherlands
Naarden, The Netherlands, 20-22 April 2012
During the weekend of 20th to 22nd April 2012 seventeen clinical and basic scientists and a patient representative met in Naarden, The Netherlands to discuss Complex I deficiency. Delegates work in six ENMC member countries (Finland, France, Germany, Italy, the Netherlands and the UK) and three non-member countries (Australia, Canada and Israel). The meeting was the first ENMC workshop dedicated to Complex I deficiency, the most common subgroup of mitochondrial diseases.
Background and Aims of the Workshop
Mitochondria are the cell’s powerplants and contain more than one thousand different proteins, many of which are essential for producing energy inside the cell. Disorders of mitochondrial energy generation are the most common inherited metabolic disorders. Five enzymes are critical for mitochondrial energy production and genetic defects of the first and largest of these enzymes, known as complex I or NADH:ubiquinone oxidoreductase, cause about one third of all mitochondrial diseases, particularly those presenting early in childhood. Currently fewer than half of patients with complex I deficiency receive a genetic diagnosis, and there are no curative treatments.
Outcomes of the Workshop
During the workshop, we discussed:
- current knowledge regarding the structure, function and assembly of the complex I enzyme
- methods for biochemical assessment of complex I deficiency
- known genetic defects associated with complex I deficiency (33 genes coding for components of the enzyme or factors required for its correct assembly within the mitochondrial membrane)
- new high throughput genetic diagnostic tools
- new mouse models for studying disease mechanisms and preclinical trials
- approaches to treatment for complex I deficient patients
How this Will Benefit Patients
Recent progress in identifying genetic causes (such as exome sequencing) offer the prospect of transforming the speed and effectiveness of genetic diagnosis for affected families. The importance of retaining close interaction between clinical, biochemical and genetic teams to ensure robust and accurate diagnoses was emphasised. New mouse models of complex I deficiency offer great potential for understanding this highly complex and puzzling group of diseases, and are the first step in developing new treatments for transfer into the clinic.