Browse by author
Lookup NU author(s): Professor Wyatt YueORCiD, Dr Sabrina MackinnonORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Succinyl-CoA:3-oxoacid coenzyme A transferase deficiency (SCOTD) is a rare autosomal recessive disorder of ketone body utilization caused by mutations in OXCT1. We performed a systematic literature search and evaluated clinical, biochemical and genetic data on 34 previously published and 10 novel patients with SCOTD. Structural mapping and in silico analysis of protein variants is also presented. All patients presented with severe ketoacidotic episodes. Age at first symptoms ranged from 36 h to 3 years (median 7 months). About 70% of patients manifested in the first year of life, approximately one quarter already within the neonatal period. Two patients died, while the remainder (95%) were alive at the time of the report. Almost all the surviving patients (92%) showed normal psychomotor development and no neurologic abnormalities. A total of 29 missense mutations are reported. Analysis of the published crystal structure of the human SCOT enzyme, paired with both sequence-based and structure-based methods to predict variant pathogenicity, provides insight into the biochemical consequences of the reported variants. Pathogenic variants cluster in SCOT protein regions that affect certain structures of the protein. The described pathogenic variants can be viewed in an interactive map of the SCOT protein at https://michelanglo.sgc.ox.ac.uk/r/oxct. This comprehensive data analysis provides a systematic overview of all cases of SCOTD published to date. Although SCOTD is a rather benign disorder with often favourable outcome, metabolic crises can be life-threatening or even fatal. As the diagnosis can only be made by enzyme studies or mutation analyses, SCOTD may be underdiagnosed.
Author(s): Grünert SC, Foster W, Schumann A, Lund A, Pontes C, Roloff S, Weinhold N, Yue WW, AlAsmari A, Obaid OA, Faqeih EA, Stübbe L, Yamamoto R, Gemperle-Britschgi C, Walter M, Spiekerkoetter U, Mackinnon S, Sass JO
Publication type: Article
Publication status: Published
Journal: Biochimie
Year: 2021
Volume: 183
Pages: 55-62
Print publication date: 01/04/2021
Online publication date: 14/02/2021
Acceptance date: 03/02/2021
ISSN (print): 0300-9084
ISSN (electronic): 1638-6183
Publisher: Elsevier
URL: https://doi.org/10.1016/j.biochi.2021.02.003
DOI: 10.1016/j.biochi.2021.02.003
PubMed id: 33596448
Altmetrics provided by Altmetric
