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Iron-sulfur Cluster ISD11 Deficiency (LYRM4 Gene) Presenting as Cardiorespiratory Arrest and 3-methylglutaconic Aciduria

2019-07-24Journal article Open access
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dc.contributor.authorCoelho, Margarida Paiva
dc.contributor.authorCorreia, Joana
dc.contributor.authorDias, Aureliano
dc.contributor.authorNogueira, Célia
dc.contributor.authorBandeira, Anabela
dc.contributor.authorMartins, Esmeralda
dc.contributor.authorVilarinho, Laura
dc.date.accessioned2020-05-08T18:47:46Z
dc.date.available2020-05-08T18:47:46Z
dc.date.issued2019-07-24
dc.descriptionFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31497476/pt_PT
dc.description.abstractIn the era of genomics, the number of genes linked to mitochondrial disease has been quickly growing, producing massive knowledge on mitochondrial biochemistry. LYRM4 gene codifies for ISD11, a small protein (11 kDa) acting as an iron-sulfur cluster, that has been recently confirmed as a disease-causing gene for mitochondrial disorders. We present a 4-year-old girl patient, born from non-consanguineous healthy parents, with two episodes of cardiorespiratory arrest after respiratory viral illness with progressive decreased activity and lethargy, at the age of 2 and 3 years. She was asymptomatic between crisis with regular growth and normal development. During acute events of illness, she had hyperlactacidemia (maximum lactate 5.2 mmol/L) and urinary excretion of ketone bodies and 3-methylglutaconic acid, which are normalized after recovery. A Next Generation Sequence approach with a broad gene panel designed for mitochondrial disorders revealed a novel probably pathogenic variant in homozygosity in the LYRM4 gene [p.Tyr31Cys (c.92A>G)] with Mendelian segregation. Functional studies in the skeletal muscle confirmed a combined deficiency of the mitochondrial respiratory chain (I, II, and IV complexes). To our knowledge, this is the third case of LYRM4 deficiency worldwide and the first with 3-methylglutaconic aciduria, not reported in any Fe-S cluster deficiency. Remarkably, it appears to be no neurological involvement so far, only with life-threating acute crisis triggered by expectably benign autolimited illnesses. Respiratory chain cofactors and chaperones are a new field of knowledge and can play a remarkable effect in system homeostasis.pt_PT
dc.description.sponsorshipFundação para a Ciência e a Tecnologia, Grant/Award Number: PTDC/DTP‐PIC/2220/2014; NORTE2020, Grant/Award Number: NORTE‐01‐0246‐FEDER‐000014pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJIMD Rep. 2019 Jul 24;49(1):11-16. doi: 10.1002/jmd2.12058. eCollection 2019 Seppt_PT
dc.identifier.doi10.1002/jmd2.12058pt_PT
dc.identifier.issn2192-8304
dc.identifier.urihttp://hdl.handle.net/10400.18/6624
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/full/10.1002/jmd2.12058pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectMitochondrial Diseasespt_PT
dc.subjectLYRM4 Genept_PT
dc.subjectMitochondrial Disorder.pt_PT
dc.subject3‐methylglutaconic aciduriapt_PT
dc.subjectFe‐S clusterspt_PT
dc.subjectISD11pt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleIron-sulfur Cluster ISD11 Deficiency (LYRM4 Gene) Presenting as Cardiorespiratory Arrest and 3-methylglutaconic Aciduriapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage16pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage11pt_PT
oaire.citation.titleJIMD Reportspt_PT
oaire.citation.volume49pt_PT
rcaap.embargofctDe acordo com o editor online da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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