Longitudinal Physiological Changes in Inherited Metabolic Disorders
Research type
Research Study
Full title
Longitudinal study of aerobic capacity and skeletal muscle characteristics in patients with rare inherited metabolic disorders (IMD)
IRAS ID
303679
Contact name
Philip Hennis
Contact email
Sponsor organisation
Nottingham Trent University
ISRCTN Number
ISRCTN12192375
Duration of Study in the UK
10 years, 0 months, 0 days
Research summary
Rare inherited disorders of metabolism (IMD)such as Glycogen Storage Diseases (GSD) and fatty acid oxidation disorders (FAOD) often result in high levels of fatigue and poor exercise capacity. Cross-sectional studies within these patients have shown muscle weakness, profound exercise limitation and poor physical function (Hennis, et al. 2022). In many types, this can progress throughout adulthood until the individual is reliant on a wheelchair to mobilise. Despite wide awareness of this decline in physical function, very little longitudinal data are available. Only through large-scale longitudinal studies will we begin to fully understand the magnitude of exercise intolerance and the rate of physical decline in these patients, to then establish lifestyle factors that can impact the onset and/or severity of this decline.
Other inherited metabolic disorders which fall outside of disorders of energy metabolism and do not specifically present with a muscle phenotype also warrant further study. In PKU for example, the impact of recommended lifelong dietary restriction (Singh, Cunningham, Mofidi, et al. 2016; van Wegberg, MacDonald, Ahring, et al. 2017; Ingwood) on exercise intolerance, muscle strength and architecture and bone mineral density (BMD) is not well established. Identifying the change in these physical outcomes and assessing the impact of diet and lifestyle choices are therefore justified, particularly within a largescale longitudinal study.
As such this we have several aims:
1)Establish the longitudinal changes in aerobic capacity and skeletal muscle characteristics in patients with rare IMD.
2)Gain greater understanding of the underlying pathophysiology of the diseases.
3)Identify the impact of physical decline on markers of health and wellbeing.
4)Establish risk factors for high rates of physical decline.
This will enable us to greatly increase our understanding of rare IMD and will provide valuable information towards interventions aimed at improving exercise tolerance and the onset and/or severity of disease progression.REC name
South East Scotland REC 01
REC reference
22/SS/0069
Date of REC Opinion
26 Oct 2022
REC opinion
Further Information Favourable Opinion