News release

From: Murdoch Children's Research Institute

Vitamin B3 treatment may halt severity of rare genetic disease

Release tags: Human | Experimental study | Peer-reviewed

Research at a Glance:

• A new study co-led by Murdoch Children’s Research Institute (MCRI) and the Luxembourg Centre for Systems Biomedicine (LCSB) has found children with a rare and often fatal genetic condition may benefit from early treatment with vitamin B3, halting their significant deterioration
• The research significantly expands our knowledge of NAXD deficiency, showing that high-dose niacin therapy could improve survival outcomes
• The team also identified nine additional cases of the disorder, showing that the condition can appear in a wider range of ways than previously recognised, including problems affecting the nervous system, heart and development before birth
• The researchers said the findings could change the outlook for children living with NAXD deficiency by highlighting the importance of early recognition and intervention

Children with a rare and often fatal genetic condition may benefit from early treatment with vitamin B3, halting their significant deterioration, according to a new study.

The research, led by Murdoch Children’s Research Institute (MCRI) and the Luxembourg Centre for Systems Biomedicine (LCSB), significantly expands our knowledge of NAXD deficiency, showing that high-dose niacin therapy could improve survival outcomes.

The team also identified nine additional cases of the disorder, showing that the condition can appear in a wider range of ways than previously recognised, including problems affecting the nervous system, heart and development before birth.

The healthy form of the NAXD gene allows cells to keep making the energy our body needs. NAXD deficiency is an ultra-rare genetic disorder caused by faults in the gene. Researchers believe vitamin B3 may help support energy-producing pathways. Affected children are often born healthy, but common childhood illnesses such as influenza or COVID-19 can trigger sudden and severe complications which mostly affect the brain and heart.

Published in the Journal of Inherited Metabolic Disease,the study helped nine children receive a NAXD diagnosis, who were referred to MCRI for further testing. Encouragingly, four children who were treated with a high vitamin B3 dose survived fever and infections that could have otherwise caused serious health problems or death. Two experienced disease onset following a COVID-19 infection, highlighting the vulnerability of children with the condition to infection and the need for them to stay up to date with vaccinations.

MCRI Dr Nicole Van Bergen said the findings could change the outlook for children living with NAXD deficiency by highlighting the importance of early recognition and intervention.

“This disorder is often devastating, with children deteriorating rapidly after even mild illness,” she said. “Common infections and minor injuries can end up in life-threatening complications.

“But seeing children survive illnesses after treatment with high-dose vitamin B3 offers new hope for affected children and their families. While further research into the long-term use of vitamin B3 is needed, the condition should now be considered as a treatable disease.

“Our team is also testing medicines that are proven to increase cellular energy levels to see if they can also safely and effectively treat NAXD. This approach could provide a lower-cost alternative to developing a new drug from scratch.”

Importantly, the study also broadens our understanding of the clinical presentation of NAXD deficiency, discovering that changes in different parts of the NAXD gene were linked to distinct forms of the disease.

It found four children experienced the more typical patterns of neurological deterioration, including seizures and developmental delay following illness. Another four developed serious heart complications, while one case of severe neurodegeneration before birth resulted in stillbirth.

Dr Van Bergen said the findings may help clinicians diagnose children earlier, particularly those with additional, non-typical neurological traits and heart symptoms.

“Future research will focus on exploring these different subtypes of disease,” she said. “However, for a disease only identified in 2019, our work represents a rapid and significant step forward in understanding and treating NAXD deficiency.”

Researchers from the University of Melbourne, Nickelaus Children’s Health System, Children’s Hospital of Philadelphia, Hospital de Niños Dr. Ricardo Gutiérrez, The Children's Hospital at Westmead, University of Sydney, University Hospital Southampton NHS Foundation Trust, University of Southampton, Vietnam National Children’s Hospital and the Queensland Children’s Hospital also contributed to the research.