Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria
Abstract 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 di...
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| Format: | Article |
| Language: | English |
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Wiley
2019-09-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12058 |
| _version_ | 1819089993773088768 |
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| author | Margarida Paiva Coelho Joana Correia Aureliano Dias Célia Nogueira Anabela Bandeira Esmeralda Martins Laura Vilarinho |
| author_facet | Margarida Paiva Coelho Joana Correia Aureliano Dias Célia Nogueira Anabela Bandeira Esmeralda Martins Laura Vilarinho |
| author_sort | Margarida Paiva Coelho |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T22:16:46Z |
| format | Article |
| id | doaj.art-c9ae8f1531444b8b8bb4b39c32c3ead2 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-21T22:16:46Z |
| publishDate | 2019-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-c9ae8f1531444b8b8bb4b39c32c3ead22022-12-21T18:48:26ZengWileyJIMD Reports2192-83122019-09-01491111610.1002/jmd2.12058Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduriaMargarida Paiva Coelho0Joana Correia1Aureliano Dias2Célia Nogueira3Anabela Bandeira4Esmeralda Martins5Laura Vilarinho6Reference Center for Metabolic Disorders Centro Hospitalar Universitário do Porto Porto PortugalReference Center for Metabolic Disorders Centro Hospitalar Universitário do Porto Porto PortugalNewborn Screening, Metabolism and Genetics Unit, Human Genetics Department National Institute of Health Doutor Ricardo Jorge Lisboa PortugalNewborn Screening, Metabolism and Genetics Unit, Human Genetics Department National Institute of Health Doutor Ricardo Jorge Lisboa PortugalReference Center for Metabolic Disorders Centro Hospitalar Universitário do Porto Porto PortugalReference Center for Metabolic Disorders Centro Hospitalar Universitário do Porto Porto PortugalNewborn Screening, Metabolism and Genetics Unit, Human Genetics Department National Institute of Health Doutor Ricardo Jorge Lisboa PortugalAbstract 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.https://doi.org/10.1002/jmd2.120583‐methylglutaconic aciduriaFe‐S clustersISD11LYRM4mitochondrial disorder |
| spellingShingle | Margarida Paiva Coelho Joana Correia Aureliano Dias Célia Nogueira Anabela Bandeira Esmeralda Martins Laura Vilarinho Iron‐sulfur cluster ISD11 deficiency (LYRM4 gene) presenting as cardiorespiratory arrest and 3‐methylglutaconic aciduria JIMD Reports 3‐methylglutaconic aciduria Fe‐S clusters ISD11 LYRM4 mitochondrial disorder |
| 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 | 3‐methylglutaconic aciduria Fe‐S clusters ISD11 LYRM4 mitochondrial disorder |
| url | https://doi.org/10.1002/jmd2.12058 |
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