A 22-month-old female child of a consanguineous marriage presented with recurrent nausea, diarrhea, elevated liver enzymes, metabolic acidosis, and developmental regression. Urine analysis revealed elevated 3-methylglutaric acid and 3-methylglutaconic acid. Brain MRI showed bilateral basal ganglia injury (Figure, A–C) and cerebellar atrophy (Figure, D). Auditory brainstem response assessment demonstrated bilateral profound sensorineural hearing loss. DNA analysis revealed a pathogenic homozygous variant of the SERAC1 gene, diagnostic of methylglutaconic aciduria, deafness, encephalopathy, Leigh-like (MEGDEL) syndrome.
Axial T2-weighted image (A) showing symmetrical T2 hyperintensity with atrophy of the caudate nuclei (short arrows) and T2 hyperintensity of the putamina with sparing of their mid-dorsal portions (long arrows). Axial diffusion image (B) and ADC map (C) showing mixed diffusion characteristics in the areas of injury: restricted diffusion (long arrows, sites of active injury) and facilitated diffusion (short arrows). Coronal T2-weighted image (D) showing cerebellar atrophy (arrow). ADC = apparent diffusion coefficient; MEGDEL = methylglutaconic aciduria, deafness, encephalopathy, Leigh-like syndrome.
MEGDEL syndrome is an infantile-onset syndrome characterized by dystonia, deafness, progressive spasticity, developmental delay or regression, and 3-methylglutaconic aciduria. The causative SERAC1 gene encodes a phosphatidylglycerol remodeler, essential for mitochondrial function and intracellular cholesterol trafficking. When imaging at the appropriate stage (1–4 years of age), the pattern of basal ganglia injury on T2-weighted images sparing the mid-dorsal putamina, called “putaminal eyes,” is pathognomonic.1 Life expectancy is unknown. Some patients die in infancy.
Author Contributions
R. Altamimi: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. H. Aldhalaan: drafting/revision of the manuscript for content, including medical writing for content. E. Tous: drafting/revision of the manuscript for content, including medical writing for content. M. Nicolas-Jilwan: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data.
Study Funding
No targeted funding reported.
Disclosure
The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
Footnotes
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Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
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Submitted and externally peer reviewed. The handling editor was Resident & Fellow Section Deputy Editor Ariel Lyons-Warren, MD, PhD.
- Received April 6, 2023.
- Accepted in final form July 10, 2023.
- Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
