Journal article
Expanding the clinical and radiological phenotypes of leukoencephalopathy due to biallelic HMBS mutations
CA Stutterd, A Kidd, C Florkowski, E Janus, M Fanjul, A Raizis, TY Wu, J Archer, RJ Leventer, DJ Amor, V Lukic, M Bahlo, P Gow, PJ Lockhart, MS van der Knaap, MB Delatycki
American Journal of Medical Genetics Part A | WILEY | Published : 2021
DOI: 10.1002/ajmg.a.62377
Abstract
Pathogenic heterozygous variants in HMBS encoding the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase, cause acute intermittent porphyria (AIP). Biallelic variants in HMBS have been reported in a small number of children with severe progressive neurological disease and in three adult siblings with a more slowly, progressive neurological disease and distinct leukoencephalopathy. We report three further adult individuals who share a distinct pattern of white matter abnormality on brain MRI in association with biallelic variants in HMBS, two individuals with homozygous variants, and one with compound-heterozygous variants. We present their clinical and radiol..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank the individuals and their families for their participation in this research. Chloe A Stutterd was supported by the Royal Children's Hospital/Murdoch Children's Research Institute Flora Suttie Neurogenetics Fellowship made possible by the Suttie Family and their supporters, the Thyne-Reid Foundation and the Macquarie Foundation. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors. Melanie Bahlo was supported by the Australian Government National Health and Medical Research Council (NHMRC) with a Program Grant (1054618) and a Senior Research Fellowship (1102971). Additional funding was provided by the Independent Research Institute Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Program. Richard J. Leventer is supported by a Melbourne Children's Clinician Scientist Fellowship. Paul J Lockhart is supported by the Vincent Chiodo Foundation.