非ケトーシス型高グリシン血症

Nonketotic hyperglycemic hemichorea is a rare neurological disorder. Neuroimaging may provide supportive evidence, typically demonstrating contralateral basal ganglia abnormalities corresponding to the side of involuntary movements. However, characteristic findings may be absent or highly subtle in some patients, which can complicate recognition and delay diagnosis. Herein, we report the case of a 76-year-old woman without a known history of diabetes mellitus who presented with a 7-day history of involuntary choreiform movements of the right hand. On admission, initial brain computed tomography was interpreted as unremarkable; however, retrospective review revealed a subtle, faint hyperdensity in the left striatum. Magnetic resonance imaging, including diffusion-weighted imaging, showed no obvious characteristic signal changes in the basal ganglia. Laboratory testing demonstrated marked hyperglycemia without ketosis. After alternative etiologies were excluded, the presentation was considered most consistent with nonketotic hyperglycemic hemichorea based on the clinical syndrome and metabolic profile. The patient's symptoms improved markedly after intensive glycemic control with insulin therapy. This case highlights that nonketotic hyperglycemic hemichorea should be considered in patients with acute hemichorea and hyperglycemia, even when neuroimaging initially appears unremarkable, and that prompt glycemic management remains the cornerstone of treatment.

What is already known about this topic? ◦. Nonketotic Hyperglycinemia is a severe metabolic disorder caused by disease‐causing variants in GLDC or AMT. ◦. Carrier screening does not universally report variants of uncertain significance (VUS). ◦. Genetic counseling is essential for informed reproductive decision‐making. What does this study add? ◦. Highlights the impact of unreported VUS in carrier screening, and the need for accurate variant interpretation and counseling. ◦. Suggests disclosing a partner's VUS to enhance informed decision‐making when another partner carries a pathogenic or likely pathogenic variant for the same condition.

Brain energy metabolism is produced from glucose by mitochondrial oxidative phosphorylation. Variants in the mitochondrial enzyme glycine decarboxylase (GLDC) cause a rare neurological disease, nonketotic hyperglycinemia, with expected hallmarks of brain glycine elevation and responsiveness to folate deficiency but the consequences for energy mechanisms remain unknown. We find that brains of young-attenuated mutant mice show a 1.5-fold increase in glycine and no change in folate responsiveness. They are, however, reduced > 5-fold in GLDC, indicate decrease in the mitochondrial lipoyl-transfer protein GCSH and lipoylation of the pyruvate dehydrogenase complex as well as rise in signatures of astrocyte mitochondrial β-oxidation of fatty acids proportionate to mutation severity and activation of pyruvate dehydrogenase. Together these data reveal a novel GLDC mechanism that regulates catabolic mitochondrial energy processes in both attenuated and severe brain disease and suggest new targets in energy metabolism to treat nonketotic hyperglycinemia.

AIM: This study aimed to compare the clinical, biochemical, and nutritional outcomes of classical nonketotic hyperglycinemia (NKH) patients treated with a ketogenic diet (KD) versus a glycine-restricted diet (GRD). METHODS: This retrospective study included patients with classical nonketotic hyperglycinemia treated with either a KD (n = 8) or a GRD (n = 6). Seizure frequency, seizure scores, antiepileptic drug (AED) use, motor function (GMFCS-E&R), swallowing difficulties, plasma glycine levels, and nutritional parameters were evaluated before and after dietary treatment. RESULTS: Baseline characteristics did not differ significantly between groups. Post-treatment assessments showed no significant differences in GMFCS scores, swallowing function, or plasma glycine levels. However, KD resulted in significantly reduced seizure frequency and seizure scores, and decreased AED use compared with GRD. Within-group analysis showed significant seizure control in the KD group, whereas seizure frequency increased in the GRD group. An increase in LDL cholesterol was observed in KD group, as expected; other nutritional parameters remained stable. Mortality was similarly high in both groups. CONCLUSION: Neither diet altered biochemical parameters or motor outcomes. However, KD provided better seizure control compared to GRD, supporting its role as a useful adjunctive therapy in NKH.