A disorder called hereditary hemochromatosis, brought on by a gene mutation, leads to the body absorbing an excessive amount of iron, resulting in tissue damage and conditions like liver disease, heart problems and diabetes. Scant and conflicting research had suggested, nevertheless, that the brain was spared from iron accumulation by the blood-brain barrier, a network of blood vessels and tissue comprised of closely spaced cells that protects against invasive pathogens and toxins.

But in a recent study published within the August 1, 2022 online issue of JAMA Neurology, researchers at University of California San Diego, with colleagues at 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 considerable iron buildup in regions of the brain accountable for movement.

The findings suggest that the gene mutation principally accountable for hereditary hemochromatosis could also be a risk factor for developing movement disorders, corresponding to Parkinson’s disease, which is brought on by a lack of nerve cells that produce the chemical messenger dopamine.

Moreover, the researchers found that males of European descent who carry two of the gene mutations were at best risk; females weren’t.

The sex-specific effect is consistent with other secondary disorders of hemochromatosis. Males show the next disease burden than females on account of natural processes, corresponding to menstruation and childbirth that expel from the body excess iron build-up in women.”

Robert Loughnan, PhD, first creator, postdoctoral scholar, Population Neuroscience and Genetics Lab at UC San Diego

The observational study involved conducting MRI scans of 836 participants, 165 of who were at high genetic risk for developing hereditary hemochromatosis, which affects roughly 1 in 300 non-Hispanic White people, in response to the Centers for Disease Control and Prevention. The scans detected substantial iron deposits localized to motor circuits of the brain for these high risk individuals.

The researchers then analyzed data representing almost 500,000 individuals and located that males, but not females, with high genetic risk for hemochromatosis were at 1.80-fold increased risk for developing a movement disorder, with lots of these individuals not having a concurrent diagnosis for hemochromatosis.

“We hope our study can bring more awareness to hemochromatosis, as many high-risk individuals aren’t aware of the abnormal amounts of iron accumulating of their brains,” said senior corresponding creator Chun Chieh Fan, MD, PhD, an assistant adjunct professor at UC San Diego and principal investigator on the Laureate Institute for Brain Research, based in Tulsa, OK. “Screening high-risk individuals for early detection could also be helpful in determining when to intervene to avoid more severe consequences.”

Loughnan said the findings have immediate clinical import because there exist already protected and approved treatments to scale back excess iron resulting from the gene mutation. Moreover, the brand new data may result in further revelations about how iron accumulates within the brain and increases the chance of movement disorders.

Roughly 60,000 Americans are diagnosed with Parkinson’s disease annually, with 60 percent being male. Late-onset Parkinson’s disease (after the age of 60) is most typical, but rates are rising amongst younger adults.

More broadly, an estimated 42 million people in the US suffer from some type of movement disorder, corresponding to essential tremor, dystonia and Huntington’s disease.

Source:

University of California – San Diego

Journal reference:

Loughnan, R., et al. (2022) Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders. JAMA Neurology. doi.org/10.1001/jamaneurol.2022.2030.