Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome

Wortmann SB 1 , van Hasselt PM 2 , Barić I 3 , Burlina A 4 , Darin N 5 , Hörster F 6 Show all authors , Coker M 7 , Ucar SK 7 , Krumina Z 8 , Naess K 9 , Ngu LH 10 , Pronicka E 11 , Riordan G 12 , Santer R 13 , Wassmer E 14 , Zschocke J 15 , Schiff M 16 , de Meirleir L 17 , Alowain MA 18 , Smeitink JA 1 , Morava E 19 , Kozicz T 20 , Wevers RA 21 , Wolf NI 22 , Willemsen MA 23

Affiliations 

  • 1 Department of Pediatrics, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands
  • 2 Department of Metabolic Diseases, Wilhelmina Children's Hospital Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands
  • 3 Department of Pediatrics, University Hospital Centre Zagreb and University of Zagreb, School of Medicine, Zagreb, Croatia
  • 4 Division of Inherited Metabolic Diseases, Department of Pediatrics, University Hospital of Padua, Padua, Italy
  • 5 Department of Pediatrics, University of Gothenburg, The Queen Silvia's Children Hospital, Gothenburg, Sweden
  • 6 Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Heidelberg, Germany
  • 7 Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey
  • 8 Medical Genetics Clinic, Children's University Hospital, Riga, Latvia
  • 9 Department of Pediatric Neurology, Karolinska University Hospital, Stockholm, Sweden
  • 10 Division of Clinical Genetics, Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
  • 11 Department of Metabolic Diseases, Children's Memorial Health Institute, Warsaw, Poland
  • 12 Department of Pediatric Neurology, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa
  • 13 Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 14 Birmingham Children's Hospital, Birmingham, United Kingdom
  • 15 Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria
  • 16 Reference Center for Inborn Errors of Metabolism, Hôpital Robert Debré, APHP, INSERM U1141 and Université Paris-Diderot, Sorbonne Paris Cité, Paris, France
  • 17 Pediatric Neurology and Metabolic Diseases, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussels, Belgium
  • 18 Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  • 19 Hayward Genetics Center and Department of Pediatrics, Tulane University Medical School, New Orleans, LA, United States
  • 20 Department of Anatomy, Radboudumc, Nijmegen, The Netherlands
  • 21 Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases (LGEM), Radboudumc, Nijmegen, The Netherlands
  • 22 Department of Child Neurology, VU University Medical Center, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
  • 23 Department of Neurology, Radboudumc, Nijmegen, The Netherlands
Neuropediatrics, 2015 Apr;46(2):98-103.
PMID: 25642805 DOI: 10.1055/s-0034-1399755

Abstract

Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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