A condition called hereditary hemochromatosis, caused by a gene mutation, causes the body to absorb too much iron, leading to tissue damage and conditions such as liver disease, heart problems, and diabetes. Little and contradictory research, however, had previously suggested that the brain was spared iron accumulation by the blood-brain barrier, a network of blood vessels and tissue made up of closely spaced cells that protects against invasive pathogens and toxins.
But in a new study published in the August 1, 2022 online issue of JAMA NeurologyResearchers at the University of California San Diego, with colleagues from UC San Francisco, Johns Hopkins Bloomberg School of Public Health and Laureate Institute for Brain Research, report that individuals with two copies of the gene mutation (one inherited from each parent) show evidence of significant iron accumulation in areas of the brain responsible for movement.
The findings suggest that the gene mutation primarily responsible for hereditary hemochromatosis 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.
In addition, the researchers found that men of European descent who carry two of the gene mutations were most at risk; females were not.
“The sex-specific effect is consistent with other secondary disorders of hemochromatosis,” said first author Robert Loughnan, Ph.D., a postdoctoral researcher in the Population Neuroscience and Genetics Lab at UC San Diego. “Men show a higher burden of disease than women due to natural processes, such as menstruation and childbirth that expel excess iron build-up in women from the body.”
The observation study involved in performing MRI scans of 836 participants, 165 of whom were at high genetic risk for developing hereditary hemochromatosis, which affects about 1 in 300 non-Hispanic whites, according to the Centers for Disease Control and Prevention. The scans detected significant iron deposits located in motor circuits of the brain for these high-risk individuals.
The researchers then analyzed data representing nearly 500,000 individuals and found that men, but not women, at high genetic risk for hemochromatosis had a 1.80-fold increased risk of developing a movement disorder, with many of these individuals not being diagnosed at the same time. for hemochromatosis.
“We hope our study can bring more awareness to hemochromatosis, as many high-risk individuals are unaware of the abnormal amounts of iron that accumulate in their brains,” said senior corresponding author Chun Chieh Fan, MD, Ph.D. ., an assistant adjunct professor at UC San Diego and principal investigator at the Laureate Institute for Brain Research, located in Tulsa, OK. “Screening individuals at high risk for early detection may be helpful in determining when to intervene to prevent more serious consequences.”
Loughnan said the findings have immediate clinical significance because safe and approved treatments already exist to reduce excess iron from the gene mutation. In addition, the new data could lead to further revelations about how iron accumulates in the brain and the risk of movement disorders.
About 60,000 Americans are diagnosed with Parkinson’s disease each year, 60 percent of whom are men. Late-onset Parkinson’s disease (after age 60) is most common, but the number is increasing in younger adults.
More broadly, an estimated 42 million people in the United States suffer from some form of movement disorder, 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; Leo Sugrue, UC San Francisco; Mary E.T. Boyle, UC San Diego and Johns Hopkins Bloomberg School of Public Health; and Wesley K. Thompson at UC San Diego and Laureate Institute for Brain Research.
Robert Loughnan et al, Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders, JAMA Neurology (2022). DOI: 10.1001/jamaneurol.2022.2030
University of California – San Diego
Quote: Brain Iron Accumulation Linked to Higher Risk of Movement Disorders (2022, Aug 1,), retrieved Aug 1, 2022 from https://medicalxpress.com/news/2022-08-iron-buildup-brain-linked-higher.html
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