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 iron accumulation by the blood-brain barrier, a network of blood vessels and tissue composed of closely spaced cells that protects against invading pathogens and toxins.
But in a new study published in the August 1, 2022, online issue of JAMA Neurology, researchers from the University of California, San Diego, with colleagues from the UC San Francisco, Johns Hopkins Bloomberg School of Public Health and Laureate Institute for Brain Research, report that people with two copies of the gene mutation (one inherited from each parent) show evidence of substantial iron accumulation in brain regions responsible for movement.
The results 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 at greater risk; women were not.
“The sex-specific effect is consistent with other secondary disorders of hemochromatosis,” said first author Robert Loughnan, PhD, a postdoctoral researcher in the Laboratory of Neuroscience and Population Genetics at UC San Diego. “Men show a higher burden of disease than women because of natural processes, such as menstruation and childbirth, that flush excess iron from the body in women.”
The observational study involved MRI scans of 836 participants, 165 of whom had a high genetic risk of developing hereditary hemochromatosis, which affects about 1 in 300 non-Hispanic white people, according to the Centers for Disease Control and Prevention. Disease Prevention. The scans detected substantial iron deposits located in the 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, with a high genetic risk for hemochromatosis had a 1.80 times greater risk of developing a movement disorder, and many of these people did not have a concurrent diagnosis of hemochromatosis.
“We hope our study can bring more awareness to hemochromatosis, as many high-risk people are unaware of abnormal amounts of iron accumulating in their brains,” said corresponding lead author Chun Chieh Fan, MD, PhD, adjunct assistant professor at UC San Diego and principal investigator at the Laureate Institute for Brain Research, based in Tulsa, OK. “Screening high-risk individuals for early detection may be useful in determining when to intervene to prevent more serious consequences.”
Loughnan said the findings have immediate clinical significance because safe, approved treatments already exist to reduce excess iron resulting from the gene mutation. In addition, the new data may lead to further revelations about how iron accumulates in the brain and increases the risk of movement disorders.
Approximately 60,000 Americans are diagnosed with Parkinson’s disease annually, 60 percent of whom are men. Late-onset Parkinson’s disease (after age 60) is most common, but rates are increasing among younger adults.
More generally, an estimated 42 million people in the United States suffer from some form of movement disorder, including essential tremors, 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 ET 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.