Review Suggests Abnormal Manganese Processing May Impact Batten Disease Progression

Abnormal processing of the trace element manganese may impact the onset or progression of Batten disease, according to a researcher at the University of Melbourne in Australia.

In a review titled “Manganese in manganism, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Batten disease: A narrative review,” Dr. Owen Proudfoot examined the evidence that excessive levels of manganese may contribute to a range of neurodegenerative conditions.

This idea stems from the descriptions of a neurodegenerative condition called manganism, Proudfoot wrote in the article, published in the journal Neurology India.

Low levels of manganese are crucial for normal brain development. But excessive amounts may have the opposite effect.

People exposed to high levels through their occupations or through manganese-contaminated drinking water lose weight and develop mood swings, irritability, reduced attention, and slow response times. Later on, various movement symptoms appear.

The field of manganese research, however, is complicated by the rarity of the condition, Proudfoot pointed out. This makes the reliability of studies — often case reports or small case series — rather poor.

Still, the studies have inspired researchers to examine whether the trace element contributes to other neurodegenerative conditions.

Studies of mice and sheep models of Batten disease, also called juvenile neuronal ceroid lipofuscinosis, suggest that manganese processing may be linked to disease progression.

One mouse study found increased levels of the enzyme manganese superoxide dismutase in a brain area called the thalamus. The enzyme acts as an antioxidant, making researchers suggest that the disease is linked to excessive oxidative processes. But the study did not actually measure the compound in the mouse brains.

Another study, however, did. It examined three mouse models of Batten having faulty CLN1, CLN3, or CLN5 genes. In the CLN1 and CLN5 models, researchers found increased levels of manganese in the central nervous system. They saw no such changes in the CLN3 model.

In another study with a Batten sheep model, researchers found increased manganese levels in several brain areas affected by neurodegeneration. While they also discovered changes in several molecular pathways, they did not link the observations to the increase in manganese levels. They did also not detect increased levels in other examined tissues.

The findings do not convince all researchers, however. Some say there is too little evidence to draw firm conclusions from these studies.