Thompson Zachary E, Boyd Natalie K, Khoshnood Mellad M, Santoro Jonathan D
Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.
Am J Med Genet A. 2023 Dec;191(12):2868-2872. doi: 10.1002/ajmg.a.63376. Epub 2023 Aug 17.
Thiamine pyrophosphate (TPP), the substrate of Thiamine pyrophosphate kinase (TPK), is an important cofactor in carbohydrate metabolism, specifically as a cofactor of the Pyruvate dehydrogenase complex (PDH) complex. The nervous system is particularly dependent on TPP due to its reliance on glucose metabolism. In this case, a four-year-old girl had a previously unreported pathogenic variant of the gene encoding TPK (TPK1) which presented as Thiamine metabolism dysfunction syndrome 5 (THMD5; OMIM 614458). She had been diagnosed with acute disseminated encephalomyelitis and autism spectrum disorder (ASD), and initially presented with fever and agitation following vaccinations. After follow-up with genetic testing, our patient was found to have compound heterozygous pathogenic variants of TPK1. After treatment with biotin and thiamine her clinical status improved, and her ASD features resolved. The presentation of our patient was consistent with previous reports and adds to the evidence that thiamine and biotin are effective treatments of TPK1 related metabolic deficiencies. The improvement of neurobehavioral symptoms in this case was marked, highlighting the importance of early identification and therapeutic intervention in this condition.
硫胺素焦磷酸（TPP）是硫胺素焦磷酸激酶（TPK）的底物，是碳水化合物代谢中的一种重要辅助因子，特别是作为丙酮酸脱氢酶复合体（PDH）的辅助因子。由于神经系统依赖葡萄糖代谢，所以对TPP尤为依赖。在本病例中，一名4岁女孩存在先前未报道的编码TPK的基因（TPK1）的致病变异，表现为硫胺素代谢功能障碍综合征5（THMD5；OMIM 614458）。她曾被诊断为急性播散性脑脊髓炎和自闭症谱系障碍（ASD），最初在接种疫苗后出现发热和烦躁。经过基因检测随访，我们的患者被发现有TPK1的复合杂合致病变异。经生物素和硫胺素治疗后，她的临床状况有所改善，ASD特征也得以缓解。我们患者的表现与先前报道一致，并进一步证明硫胺素和生物素是治疗TPK1相关代谢缺陷的有效方法。该病例中神经行为症状的改善非常明显，突出了早期识别和治疗干预在这种疾病中的重要性。
