Eyes on MEGDEL

Distinctive basal ganglia involvement in dystonia deafness syndrome

Saskia B. Wortmann, Peter M. Van Hasselt, Ivo Barić, Alberto Burlina, Niklas Darin, Friederike Hörster, Mahmut Coker, Sema Kalkan Ucar, Zita Krumina, Karin Naess, Lock H. Ngu, Ewa Pronicka, Gilian Riordan, Rene Santer, Evangeline Wassmer, Johannes Zschocke, Manuel Schiff, Linda De Meirleir, Mohammed A. Alowain, Jan A.M. Smeitink & 5 others Eva Morava-Kozicz, Tamas Kozicz, Ron A. Wevers, Nicole I. Wolf, Michel A. Willemsen

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)98-103
Number of pages6
JournalNeuropediatrics
Volume46
Issue number2
DOIs
StatePublished - Feb 4 2015
Externally publishedYes

Fingerprint

Basal Ganglia
Magnetic Resonance Imaging
Putamen
Leigh Disease
Phosphatidylglycerols
Globus Pallidus
Caudate Nucleus
Movement Disorders
Brain Diseases
Deafness
Cholesterol
Mohr-Tranebjaerg syndrome
Pediatrics
Phenotype
Mutation
Brain
Enzymes
3-Methylglutaconic Aciduria

Keywords

  • 3-methylglutaconic aciduria
  • basal ganglia involvement
  • Leigh syndrome
  • MEGDEL syndrome
  • putamen
  • SERAC1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Wortmann, S. B., Van Hasselt, P. M., Barić, I., Burlina, A., Darin, N., Hörster, F., ... Willemsen, M. A. (2015). Eyes on MEGDEL: Distinctive basal ganglia involvement in dystonia deafness syndrome. Neuropediatrics, 46(2), 98-103. https://doi.org/10.1055/s-0034-1399755

Eyes on MEGDEL : Distinctive basal ganglia involvement in dystonia deafness syndrome. / Wortmann, Saskia B.; Van Hasselt, Peter M.; Barić, Ivo; Burlina, Alberto; Darin, Niklas; Hörster, Friederike; Coker, Mahmut; Kalkan Ucar, Sema; Krumina, Zita; Naess, Karin; Ngu, Lock H.; Pronicka, Ewa; Riordan, Gilian; Santer, Rene; Wassmer, Evangeline; Zschocke, Johannes; Schiff, Manuel; De Meirleir, Linda; Alowain, Mohammed A.; Smeitink, Jan A.M.; Morava-Kozicz, Eva; Kozicz, Tamas; Wevers, Ron A.; Wolf, Nicole I.; Willemsen, Michel A.

In: Neuropediatrics, Vol. 46, No. 2, 04.02.2015, p. 98-103.

Research output: Contribution to journalArticle

Wortmann, SB, Van Hasselt, PM, Barić, I, Burlina, A, Darin, N, Hörster, F, Coker, M, Kalkan Ucar, S, Krumina, Z, Naess, K, Ngu, LH, Pronicka, E, Riordan, G, Santer, R, Wassmer, E, Zschocke, J, Schiff, M, De Meirleir, L, Alowain, MA, Smeitink, JAM, Morava-Kozicz, E, Kozicz, T, Wevers, RA, Wolf, NI & Willemsen, MA 2015, 'Eyes on MEGDEL: Distinctive basal ganglia involvement in dystonia deafness syndrome', Neuropediatrics, vol. 46, no. 2, pp. 98-103. https://doi.org/10.1055/s-0034-1399755
Wortmann SB, Van Hasselt PM, Barić I, Burlina A, Darin N, Hörster F et al. Eyes on MEGDEL: Distinctive basal ganglia involvement in dystonia deafness syndrome. Neuropediatrics. 2015 Feb 4;46(2):98-103. https://doi.org/10.1055/s-0034-1399755
Wortmann, Saskia B. ; Van Hasselt, Peter M. ; Barić, Ivo ; Burlina, Alberto ; Darin, Niklas ; Hörster, Friederike ; Coker, Mahmut ; Kalkan Ucar, Sema ; Krumina, Zita ; Naess, Karin ; Ngu, Lock H. ; Pronicka, Ewa ; Riordan, Gilian ; Santer, Rene ; Wassmer, Evangeline ; Zschocke, Johannes ; Schiff, Manuel ; De Meirleir, Linda ; Alowain, Mohammed A. ; Smeitink, Jan A.M. ; Morava-Kozicz, Eva ; Kozicz, Tamas ; Wevers, Ron A. ; Wolf, Nicole I. ; Willemsen, Michel A. / Eyes on MEGDEL : Distinctive basal ganglia involvement in dystonia deafness syndrome. In: Neuropediatrics. 2015 ; Vol. 46, No. 2. pp. 98-103.
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AU - Darin, Niklas

AU - Hörster, Friederike

AU - Coker, Mahmut

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