Disorders of pyruvate metabolism, Krebs cycle defects, mitochondrial oxidative phosphorylation disorders, disorders of thiamine transport and metabolism
Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism impair the production of ATP, which is essential for the homeostasis and functioning of the human cell. More than 300 genes are responsible for the maintenance of normal mitochondrial function. Due to the central role of pyruvate in several metabolic pathways, defects in its metabolism impact organs and tissues that require high energy consumption, including the brain, skeletal muscle, liver, kidneys, and retina.
The clinical manifestations of this group of disorders can vary widely, ranging from developmental delay, hypotonia, cerebral atrophy, and lactic acidosis to hearing loss.
Additionally, the diseases can present with different degrees of severity, from lethal forms in newborns to milder forms in the elderly.
Diagnosis is not straightforward, given that a single disease can present with a multitude of symptoms, and a single symptom can be linked to multiple mitochondrial diseases.
Respiratory chain complexes can be analysed by a few highly specialised laboratories across Europe. While treatment options are still limited, several clinical trials are underway in search of effective therapies.
Objectives
The Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism subnetwork within MetabERN aims to:
- gain an overview of patients with Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU (e.g. which diseases, how many patients, clinical outcome, etc.).
- promote awareness towards Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU.
- facilitate the more rapid diagnosis of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU as often a significant diagnostic delay is still present.
- improve and standardize management of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases in the EU.
- improve prospects of patients with Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism disease in the EU by initiating and contributing to research and implementation of innovative therapies.
Organizational structure
The Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism subnetwork will consist of participating HCPs within the MetabERN with expertise in the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases and will build on or seek collaboration with existing international collaborations and networks of HCPs in the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases. Working groups will be formed to address different important topics within the field of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases.
These include:
- Prevention & Screening for Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases.
- Diagnosis of (new) Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases (including identification of biomarkers).
- Management of Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism diseases (development of clinical guidelines & care paths).
- Epidemiology & Outcome (participation in existing and development of new registries).
- Education and Training (development of E-learning tools, work-shops and courses).
- Virtual Counselling (for specific diseases at different HCPs with specific expertise).
- Patient Empowerment (organization of patient meetings and interaction with patient organizations).
- Research (fundamental, translational, clinical).
The executive board of the Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism subnetwork will be formed by the chairpersons of the working groups. An advisory board (with members of patients organizations, policy makers, etc) will be appointed to monitor the different activities of the Disorders of pyruvate metabolism, mitochondrial oxidative disorders, thiamine transport and metabolism subnetwork.
Coordinators
Patient Representative
