Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.

Abstract

3-Methylglutaconic aciduria (3-MGCA) type IV is defined as a heterogeneous group of inborn errors featuring in common 3-MGCA and associated with primary mitochondrial dysfunction leading to a spectrum of multisystem conditions. We studied four patients who presented at birth with a clinical picture simulating a primary mitochondrial hepatic disorder consistent with the MEGDEL syndrome including 3-MGCA, sensorineural deafness, encephalopathy and a brain magnetic resonance imaging with signs of Leigh disease. All affected children displayed biochemical features consistent with mitochondrial OXPHOS dysfunction including hepatic mitochondrial DNA depletion in one patient. Homozygosity mapping identified a candidate locus on 6q25.2-6q26. Using whole exome sequencing, we identified two novel homozygous mutations in SERAC1 recently reported to harbor mutations in MEGDEL syndrome. Both mutations were found to lead to decreased or absent expression of SERAC1. The present findings indicate that infantile hepatopathy is a cardinal feature of MEGDEL syndrome. We thus propose to rename the disease MEGDHEL syndrome.

DOI: 10.1002/ajmg.a.36059

8 Figures and Tables

01002003002014201520162017
Citations per Year

280 Citations

Semantic Scholar estimates that this publication has 280 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Sarig2013InfantileMH, title={Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.}, author={Ofer Sarig and Dorit Goldsher and Janna Nousbeck and Dana Fuchs-Telem and Ksenya Cohen-Katsenelson and Theodore C. Iancu and Irena Manov and Ann Saada and Eli Sprecher and H. George Mandel}, journal={American journal of medical genetics. Part A}, year={2013}, volume={161A 9}, pages={2204-15} }