Submitted by Dr R. Inchingolo on Thu, 27/02/2020 - 11:35
In a report published in the New England Journal of Medicine, Dr Andrew Murray and Dr Katie O’Brien of PDN, along with an international team of collaborators, describe new aspects of the human metabolic response to low oxygen levels
“For many years, we have been interested in the way in which human energy metabolism is adjusted in response to a diminished supply of oxygen,“ said Dr Murray. “As a research group, we have studied this at high altitude and in critically ill patients, scenarios in which a lack of oxygen can occur, but in both of these cases the response can be confounded by other challenges to a subject’s physiology.”
The group were presented with a unique opportunity to look at this response in a new setting when they were approached by colleagues at Kings College London and the University of Campania, Naples, Italy. The team identified a patient who had a reduced rate of growth, persistent low blood sugar, a limited exercise capacity and a very high number of red blood cells.
The team carried out genetic and protein analysis of the patient, examined their respiratory physiology in simulated high altitude, measured their exercise capacity, and performed a series of metabolic tests.
The von Hippel-Lindau (VHL) gene is fundamental for cells to survive when oxygen availability is reduced. Following genetic analysis, an alteration on the VHL gene was identified and this was associated with altered morphology and impaired function in the patient’s mitochondria, the powerhouse of the cell that uses oxygen to fuel cellular life. This reduced mitochondrial respiratory function limited the patient’s aerobic exercise capacity, compared to people without the mutation.
Dr Federico Formenti, a co-author of the study from Kings College London, commented: “The discovery of this mutation and the associated phenotype is exciting because it enables a deeper understanding of human physiology, especially in terms of how the human body senses and responds to reduced oxygen availability.”
A new syndrome has been described in which the regulation of human metabolism and skeletal muscle function, is altered. The team are now looking to study further mutations that affect oxygen sensing pathways, and the way in which these mutations alter the integrative function of the human body. Improving our understanding of these mechanisms may contribute to the treatment of more common diseases in which hypoxia is a factor.
Read the case report here.