Genetic Studies Uncover Causes of Severe Neuropathy Post-Infection

Recent genetic research has shed light on the mechanisms behind severe neuropathy that can occur following infections. A team of researchers in the UK has identified specific genetic alterations associated with a newly characterized neuropathy, providing critical insights into why some previously healthy individuals develop neuropathies after infections while others remain unaffected.

During a presentation at the annual conference of the European Society of Human Genetics, a researcher from the University of Manchester discussed a compelling case involving a child who experienced a rapid decline in health after a mild infection. Initially fit and healthy, the child was admitted to intensive care at seven months old following a fever and rash. Tragically, she passed away before her first birthday, a fate that had also befallen two of her older siblings.

In response to these alarming cases, the research team initiated a genetic discovery study. They initially identified a mutation in a gene believed to contribute to the condition, but it took nearly a decade to find another family with similar genetic changes and clinical symptoms, confirming a link between the gene and rapid neuropathy post-infection. To date, twelve families have been identified with mutations in this gene.

The genetic alterations discovered in these families exhibit similarities to the pathology observed in Guillain-Barré syndrome, a condition that can also be triggered by infections such as Epstein-Barr virus or the bacterium Campylobacter. Guillain-Barré syndrome is known for causing muscle weakness that can escalate to the point of affecting respiratory function.

The researchers express hope that their findings will illuminate the underlying mechanisms of this neuropathy. Preliminary experiments conducted on patient-derived cells suggest features akin to those seen in motor neuron disease (MND). This overlap could pave the way for reciprocal insights that benefit both conditions.

Although currently there are no effective prevention strategies for neuropathies that arise in this manner, the enhanced understanding of their genetic basis marks a significant step towards developing potential treatments. The research has also enabled quicker and more accurate diagnoses, reducing the need for extensive, costly testing. Furthermore, preconception genetic testing for at-risk individuals may inform reproductive decisions.

As awareness of their findings grows, the researchers have identified additional families globally, indicating that the condition may be more prevalent than initially thought. They are currently working on creating nerve cells from skin cells of affected individuals to delve deeper into the disorder's effects on the nervous system and to explore potential therapies.

In an innovative approach, the research team is also utilizing fruit flies to replicate their studies. They have confirmed that a single gene is responsible for this specific neuropathy, although the precise gene and its function were initially unforeseen. The identified gene plays a crucial role in regulating the transport of proteins and nucleic acids between the cell nucleus and cytoplasm, processes that are sensitive to stress, temperature fluctuations, and infections in affected patients. Such disruptions can hinder nerve repair mechanisms.

A conference chair emphasized that this research exemplifies the interaction between genetic predisposition and environmental factors, illustrating how genetic variants can heighten the risk of developing conditions in response to specific environmental triggers, such as infections.