Natural History Study of Pyruvate Dehydrogenase Deficiency

Great Ormond Street Hospital for Children NHS Foundation Trust50 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Pyruvate Dehydrogenase Complex Deficiency Pyruvate Dehydrogenase E1 Alpha Deficiency Pyruvate Dehydrogenase E1-Beta Deficiency Pyruvate Dehydrogenase E2 Deficiency Pyruvate Dehydrogenase Phosphatase Deficiency

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Newcastle Mitochondrial Disease Scale

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.

Time frame: Baseline

Central Contacts

Nandaki Keshavan, MA, MB BChir

CONTACT

020 7905 2608 n.keshavan@ucl.ac.uk

Vanshree Patel, PhD