Journal article
Severe NAD(P)HX Dehydratase (NAXD) Neurometabolic Syndrome May Present in Adulthood after Mild Head Trauma
NJ Van Bergen, K Gunanayagam, AM Bournazos, AS Walvekar, MO Warmoes, LN Semcesen, S Lunke, S Bommireddipalli, T Sikora, M Patraskaki, DL Jones, D Garza, D Sebire, S Gooley, CA McLean, P Naidoo, M Rajasekaran, DA Stroud, CL Linster, M Wallis Show all
International Journal of Molecular Sciences | Published : 2023
DOI: 10.3390/ijms24043582
Open access
Abstract
We have previously reported that pathogenic variants in a key metabolite repair enzyme NAXD cause a lethal neurodegenerative condition triggered by episodes of fever in young children. However, the clinical and genetic spectrum of NAXD deficiency is broadening as our understanding of the disease expands and as more cases are identified. Here, we report the oldest known individual succumbing to NAXD-related neurometabolic crisis, at 32 years of age. The clinical deterioration and demise of this individual were likely triggered by mild head trauma. This patient had a novel homozygous NAXD variant [NM_001242882.1:c.441+3A>G:p.?] that induces the mis-splicing of the majority of NAXD transcripts,..
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Awarded by University of Sydney
Funding Acknowledgements
The research conducted at the Murdoch Children's Research Institute (MCRI) was supported by the Victorian Government`s Operational Infrastructure Support Program. The work was supported by funding from the Mito Foundation to NVB and JC, the MCRI Near Miss grant to NVB and the MCRI Strategic Pilot Project in Stem Cell and Genomics Medicine grant to NVB and JC. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children's Hospital Foundation. The research performed at the Luxembourg Centre for Systems Biomedicine was supported by the Luxembourg National Research Fund (FNR) through the CORE grant C18/BM/12661133 to CLL and a PhD fellowship to MP within the PARK-QC doctoral training unit (PRIDE17/12244779/PARK-QC), and a donation from the Juniclair foundation to CLL. Sydney-based research was supported by Sydney Children's Hospital Foundation funding to Kids Neuroscience Centre and by a National Health and Medical Research Council (NHMRC) of Australia Senior Research Fellowship GNT1136197, Sydney Health Partners Medical Research Future Fund Rapid Applied Research Translation Program grant and Luminesce Alliance Innovation grant awarded to STC. AMB is supported by a University of Sydney Research Training Scholarship. This research was supported by grants and fellowships from the Australian National Health and Medical Research Council (GNT20097321140851 and GNT1164479). We acknowledge the Mito Foundation and the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for the provision of instrumentation, training and technical support. LS is supported by a Melbourne International Research Scholarship and the Mito Foundation PhD Top-up Scholarship. We are grateful to the Crane, Perkins and Miller families for their generous financial support.