Teaching NeuroImage: Abnormal and Persistent Mineralization of Globi Pallidi in GAMT Deficiency

Abstract: A 4-year-old boy, born to consanguineous parents, presented with global developmental delay, epilepsy, asymmetric dystonia, and autism. EEG demonstrated generalized slowing, paucity of sleep spindles, and intermittent electrodecremental response, suggesting diffuse cerebral dysfunction and epileptogenicity. Neuroimaging demonstrated T2 hyperintensities of the globi pallidi, linear T1 hyperintensities with blooming on susceptibility weighted imaging in the globi pallidi externa, and significantly reduced basal ganglia creatine peak on MRS (Figure, A–D). Whole-exome sequencing revealed a novel homozygous 2 base pair insertion in exon 2 of the GAMT gene (chr19:g.1399848_1399849insAT; (p.Cys91- TyrfsTer24)) resulting in a frameshift causing premature truncation of the protein. After 1 year of creatine supplementation, he exhibited clinical improvements in walking, seizures, and hyperactivity. Imaging demonstrated normalized creatine peaks but persistent globipallidi signal changes (Figure, E–H). This persistent globi pallidi mineralization may reflect disrupted metal homeostasis and impaired energy metabolism in the basal ganglia, an area particularly susceptible to metabolic disturbances.1,2

Link to article: https://www.neurology.org/doi/10.1212/WNL.0000000000213636

PubMed:  https://pubmed.ncbi.nlm.nih.gov/40397839/

Authors: Geetha Chanda, Ramesh Konanki, and Nihaal Reddy

Key Terms: GAMT, Clinical Study, MRS, Mutation Study, Diagnostic, Male Patient, Pediatric Patient