A disorder called hereditary hemochromatosis, caused by a genetic mutation, causes the body to absorb too much iron, leading to tissue damage and conditions such as liver disease , heart problems and diabetes. Scant and conflicting research had suggested, however, that the brain was spared from iron accumulation by the blood-brain barrier, a network of blood vessels and tissues made up of closely spaced cells that protects against invasive pathogens and diseases. toxins.
But in a new study published in the Aug. 1 2022 online issue of JAMA Neurology, researchers at the University of California, San Diego, with colleagues at UC San Francisco, the Johns Hopkins Bloomberg School of Public Health and fitness, and the Laureate Institute for Brain Investigation, report that individuals with two copies of the genetic mutation (one inherited from every dad or mum) show evidence of substantial iron accumulation in brain regions responsible for movement.
The results suggest that the genetic mutation mainly responsible for hereditary hemochromatosis for may be a risk factor for developing movement disorders, such as Parkinson’s disease, which is caused by a loss of nerve cells that produce the chemical messenger dopamine.
De Moreover, the researchers found that males of European descent who carried two of the genetic mutations were most at risk while females were not.
“The sex-specific effect is consistent with other secondary disorders of hemochromatosis,” said first author Robert Loughnan, PhD, postdoctoral researcher in the Populace Neuroscience and Genetics Lab at UC San Diego. “Men have a higher burden of disease than women due to natural processes, such as menstruation and childbirth, which expel excess iron accumulated in women from the body.”
The observational study involved performing MRI scans of 836 participants, including 165 had a high genetic risk of developing hereditary hemochromatosis, which affects approximately 1 in 300 non-Hispanic white people, according to the Centers for Disease Regulate and Prevention. The scans detected significant localized iron deposits in the motor circuits of the brain for these high-risk individuals.
Researchers then analyzed data representing nearly 500 000 people and found that men, but not women, with a high genetic risk of hemochromatosis were at a 1.80 times greater risk of developing difficulty in movement, with many of these people not having a concurrent diagnosis of hemochromatosis.
“We hope that our study can increase awareness of hemochromatosis, which many people at high risk are unaware of abnormal amounts of iron accumulating in their brains,” said senior corresponding author Chun Chieh Enthusiast, MD, PhD, adjunct assistant professor at UC San Diego and principal investigator at the Laureate Institute for Brain Investigate, based in Tu lsa, Ok. “Screening high-risk individuals for early detection can be helpful in determining when to intervene to avoid more serious consequences.”
Loughnan said the results have immediate clinical significance because there are already safe and approved treatments to reduce the excess iron resulting from the genetic mutation. Additionally, the new data could lead to new insights into how iron builds up in the brain and increases the risk of movement disorders.
Approximately 60 000 Americans are diagnosed with Parkinson’s disease each year, including 60 % are men. Late-onset Parkinson’s disease (after the age of 60 years) is the most common, but rates increase in young adults.
In addition, approximately 42 million people in the United States suffer from some form of sleep disorder. movement, such as essential tremor, dystonia, and Huntington’s disease.
Co-authors include: Jonathan Ahern, Cherisse Tompkins, Clare E. Palmer, John Iversen, Terry Jernigan and Anders Dale, all at UC San Diego Ole Andreassen, University of Oslo, Norway Léo Sugrue, UC San Francisco Mary ET Boyle, UC San Diego and Johns Hopkins Bloomberg University of Public Health and Wesley K. Thompson at UC San Diego and the Laureate Institute for Mind Research.