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Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria
In 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‐cau...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718106/ https://www.ncbi.nlm.nih.gov/pubmed/31497476 http://dx.doi.org/10.1002/jmd2.12058 |
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author | Coelho, Margarida Paiva Correia, Joana Dias, Aureliano Nogueira, Célia Bandeira, Anabela Martins, Esmeralda Vilarinho, Laura |
author_facet | Coelho, Margarida Paiva Correia, Joana Dias, Aureliano Nogueira, Célia Bandeira, Anabela Martins, Esmeralda Vilarinho, Laura |
author_sort | Coelho, Margarida Paiva |
collection | PubMed |
description | In 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. |
format | Online Article Text |
id | pubmed-6718106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67181062019-09-06 Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria Coelho, Margarida Paiva Correia, Joana Dias, Aureliano Nogueira, Célia Bandeira, Anabela Martins, Esmeralda Vilarinho, Laura JIMD Rep Case Reports In 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. John Wiley & Sons, Inc. 2019-07-24 /pmc/articles/PMC6718106/ /pubmed/31497476 http://dx.doi.org/10.1002/jmd2.12058 Text en © 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Case Reports Coelho, Margarida Paiva Correia, Joana Dias, Aureliano Nogueira, Célia Bandeira, Anabela Martins, Esmeralda Vilarinho, Laura Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title | Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title_full | Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title_fullStr | Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title_full_unstemmed | Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title_short | Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
title_sort | iron‐sulfur cluster isd11 deficiency (lyrm4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria |
topic | Case Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718106/ https://www.ncbi.nlm.nih.gov/pubmed/31497476 http://dx.doi.org/10.1002/jmd2.12058 |
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