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.
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.
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.
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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.
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