Pyruvate Dehydrogenase Complex Deficiency, Pyruvate Dehydrogenase E1 Alpha Deficiency, Pyruvate Dehydrogenase E1-Beta Deficiency, Pyruvate Dehydrogenase E2 Deficiency, Pyruvate Dehydrogenase Phosphatase Deficiency
Conditions
Keywords
PDH deficiency, Natural History, Outcomes, Prognosis, Genotype-phenotype correlation, Quality of life, Outcome measures
Brief summary
Pyruvate dehydrogenase (PDH) deficiency is one of the most common mitochondrial disorders. Patients with this genetic condition have difficulty utilising carbohydrates to produce energy and develop a combination of problems including seizures, poor balance, developmental delay, disability and have a reduced life expectancy. As for most mitochondrial disorders there is a lack of effective treatments. It is essential to understand the mechanisms underlying the disease in order to identify new treatments, and to understand the natural history of disease in order to prepare for clinical trials. To date, a natural history study of PDH deficiency has not been undertaken in the UK. The researchers aim to undertake the first natural history study of PDH deficiency in the UK, to describe the spectrum of symptoms, genetics, management and outcomes in both children and adult patients.
Interventions
None listed
Sponsors
The Freya Foundation
National Institute for Health Research, United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Compatible clinical history AND 2a Enzymatic confirmation demonstrating reduced PDH activity in patient cells or muscle tissue OR 2b Confirmed pathogenic mutation in a gene associated with primary PDH deficiency (PDHA1, PDHB, PDHX, PDP1, DLAT) OR 2c First degree relative with a confirmed pathogenic mutation causing primary PDH deficiency
Exclusion criteria
Patients with 'secondary PDH deficiency' that is patients who meet criteria 1 and 2a but who have received a genetic diagnosis which confirms pathogenic variants in a gene not associated with primary PDH deficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Newcastle Mitochondrial Disease Scale | Baseline | Newcastle Paediatric and Adult Mitochondrial Disease Scale This is a validated scoring system for mitochondrial disease patients and measures severity of disease using multiple different clinical outcome measures and questionnaires. A higher score indicates greater disease severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genetic Diagnosis | Baseline | Molecular diagnosis |
| Medical History | Baseline | Family history, past medical history |
| Disease timecourse | Baseline | Onset, symptom debut, final outcome, follow-up. |
| Neuroimaging | Baseline | MRI/MRS Head |
| Mitochondrial Disease Phenotype | Baseline | PDH deficiency Phenotype |
| Assessment of Cognitive and Developmental outcomes from source data | Baseline | Retrospective assessments documented within source data for cognitive assessments that have occurred in the past in all patients. |
| Assessment of Cognitive and Developmental outcomes at baseline | Baseline | For prospective component, cognitive assessments will be performed at baseline in adult patients only: Wechsler Test of Adult Reading (WTAR) test Symbol Search Speed of comprehension test |
| Assessment of biochemical outcome measures from source data | Baseline | This is an observational retrospective from source data and may include the following biological outcome measures: EMG, EEG, Nerve conduction Studies: Blood and CSF lactate, pyruvate, amino acids, urine organic acids, PDH enzymology, OXPHOS studies, skeletal muscle histology |
| Management | Baseline | Drug and non-drug treatments |
| Assessment of Neurophysiological outcome measures from source data | Baseline | This is an observational retrospective from source data and may include the following neurophysiological measures: EMG, EEG, Nerve conduction Studies |
Countries
United Kingdom
Contacts
Primary ContactNandaki Keshavan, MA, MB BChir
Backup ContactVanshree Patel, PhD
Outcome results
None listed