オマタ　タク   OMATA Taku   小俣　卓    所属   医学部 医学科（附属八千代医療センター）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Persistent glutamate increase in TANGO2 deficiency with normalization after vitamin supplementation: first documentation by MR spectroscopy.
掲載誌名	正式名：Orphanet journal of rare diseases 略　 称：Orphanet J Rare Dis ISSNコード：17501172/17501172
掲載区分	国外
出版社	BioMed Central
巻・号・頁	pp.10.1186/s13023-026-04338-x
著者・共著者	Taku Omata†*, Ryo Sugiyama, Yuko Shimizu-Motohashi, Jun-ichi Takanashi
担当区分	筆頭著者,責任著者
発行年月	2026/03/30
概要	Background:TANGO2 deficiency is a rare inherited metabolic disorder characterized by recurrent metabolic crises, rhabdomyolysis, arrhythmias, and encephalopathy. Recent studies suggest that TANGO2 functions as a mitochondrial lipid-acyl-CoA handling protein. Nonetheless, the cerebral metabolic abnormalities underlying neurological deterioration remain elusive. In this study, we present the first longitudinal evaluation of brain metabolism using proton magnetic resonance spectroscopy (MRS) before and after vitamin therapy, during the acute, subacute, and post-treatment phases, highlighting improved clinical manifestations following treatment. Methods:We longitudinally evaluated cerebral metabolites using MRS during the acute, subacute, and post-treatment phases. Results:A 2-year-old boy with genetically confirmed TANGO2 deficiency presented with a metabolic crisis, status epilepticus, and rhabdomyolysis (CK peak, 282,695 U/L). Despite the absence of structural abnormalities on the magnetic resonance imaging conducted on day 2, MRS revealed markedly increased glutamate (Glu; 11.51 mM; reference: 6.70 ± 0.59) with normal glutamine (Gln). On day 50, despite clinical stabilization, Glu levels remained abnormally high (9.29 mM), indicating a persistent dysfunction of the cerebral Glu–Gln cycle. Upon initiation of vitamin supplementation, including that of all eight B vitamins (i.e., B₁, B₂, B₃, B₅, B₆, B₇, B₉, and B₁₂) at the age of 3, no further crises occurred. Follow-up MRS at the age of 4 demonstrated Glu normalization (7.20 mM; reference: 6.50 ± 0.70). Conclusions:This case provides pioneering in vivo evidence of sustained cerebral Glu accumulation in a patient with TANGO2 deficiency along with improvement after metabolic therapy. Our results suggest that the impairment of energy-dependent Glu–Gln cycling and astrocytic Glu clearance might constitute a potential mechanism underlying neurological vulnerability in TANGO2 deficiency. Longitudinal MRS may allow metabolic instability and treatment responsiveness monitoring in this disorder.
DOI	10.1186/s13023-026-04338-x
PMID	41913275