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Publication
Iron-sulfur Cluster ISD11 Deficiency (LYRM4 Gene) Presenting as Cardiorespiratory Arrest and 3-methylglutaconic Aciduria
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Advisor(s)
Abstract(s)
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.
Description
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31497476/
Keywords
Mitochondrial Diseases LYRM4 Gene Mitochondrial Disorder. 3‐methylglutaconic aciduria Fe‐S clusters ISD11 Doenças Genéticas
Pedagogical Context
Citation
JIMD Rep. 2019 Jul 24;49(1):11-16. doi: 10.1002/jmd2.12058. eCollection 2019 Sep
Publisher
Wiley