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Neuropediatrics 2017; 48(05): 382-384
DOI: 10.1055/s-0037-1602833
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

MEGDEL Syndrome: Expanding the Phenotype and New Mutations

Sílvia Sequeira
1   Metabolic Unit, Department of Pediatrics, Hospital de Dona Estefânia, CHLC, Lisbon, Portugal
,
Márcia Rodrigues
2   Department of Medical Genetics, Hospital de Dona Estefânia, CHLC, Lisbon, Portugal
,
Sandra Jacinto
3   Department of Neuropediatrics, Hospital de Dona Estefânia, Centro Hospitalar Lisboa Central, Lisbon, Portugal
,
Ron A. Wevers
4   Translational Metabolic Laboratory (TML), Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Saskia B. Wortmann
5   Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), Salzburg, Austria
6   Institute of Human Genetics, Technical University Munich, Munich, Germany
7   Institute of Human Genetics, Helmholtz Zentrum Munich, Neuherberg, Germany
› Author Affiliations
Further Information

Publication History

06 January 2017

31 March 2017

Publication Date:
15 May 2017 (online)

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Abstract

3-MEthylGlutaconic aciduria, Deafness, Encephalopathy, neuroradiological evidence of Leigh-like disease (MEGDEL syndrome) was initially described in four children with additional features of defective oxidative phosphorylation. Loss of functional variants in the SERAC1 gene was later reported in relation with this disorder of phospholipid remodeling. We describe a girl born after a pregnancy complicated by intrauterine growth retardation. In the neonatal period, she presented hypotonia, lethargy, weak reflexes, transient hypoglycemia, and elevated transaminases. Magnetic resonance imaging (MRI) performed at 12 days of life showed bilateral basal ganglia alterations suggestive of Leigh syndrome. She progressed with failure to thrive, severe delay of developmental milestones, axial hypotonia, spastic tetraparesis and dystonic movements. Investigations disclosed hyperlactacidemia, and the urinary organic acids revealed high levels mainly of 3-methylglutaconic acid. Muscle biopsy showed decreased activity of several complexes of the respiratory chain. Compound heterozygosity for two previously unreported variants in SERAC1 leads to the diagnosis of MEGDEL syndrome. Unlike other patients, this child presents very early MRI alterations and manifests no deafness.

Keywords

MEGDEL syndrome - SERAC1 gene - 3-methylglutaconic aciduria - mitochondrial disorder - Leigh syndrome
 

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