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
Article first published online: 5 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 9, pages 2204–2215, September 2013
How to Cite
2013. 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. Am J Med Genet Part A 161A:2204–2215., , , , , , , , , .
Most papers in the medical literature refer to MEGDEL as an “association.” Since this condition is causality defined, I agree that this entity is a syndrome. As indicated in the paper, the authors propose calling this condition, the MEGDHEL syndrome adding the H for the hepatopathy.
John C. Carey
Conflict of interest: none.
- Issue published online: 14 AUG 2013
- Article first published online: 5 AUG 2013
- Manuscript Accepted: 19 APR 2013
- Manuscript Received: 14 SEP 2012
- MEGDEL syndrome;
- infantile hepatopathy
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. © 2013 Wiley Periodicals, Inc.