Thiamine Treatment and Favorable Outcome in an Infant with Biallelic TPK1 VariantsFunding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Episodic encephalopathy due to mutations in the thiamine pyrophosphokinase 1 (TPK1) gene is a rare autosomal recessive metabolic disorder. Patients reported so far have onset in early childhood of acute encephalopathic episodes, which result in a progressive neurologic dysfunction including ataxia, dystonia, and spasticity. Here, we report the case of an infant with TPK1 deficiency (compound heterozygosity for two previously described pathogenic variants) presenting with two encephalopathic episodes and clinical stabilization under oral thiamine and biotin supplementation. In contrast to other reported cases, our patient showed an almost normal psychomotor development, which might be due to an early diagnosis and subsequent therapy.
KeywordsTPK1 - episodic encephalopathy - thiamine-responsive disorder - genetic defect - thiamine metabolism dysfunction syndrome 5
Received: 24 December 2019
Accepted: 28 May 2020
21 October 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Mayr JA, Freisinger P, Schlachter K. et al. Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. Am J Hum Genet 2011; 89 (06) 806-812
- 2 Banka S, de Goede C, Yue WW. et al. Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations. Mol Genet Metab 2014; 113 (04) 301-306
- 3 Nosaka K, Onozuka M, Nishino H, Nishimura H, Kawasaki Y, Ueyama H. Molecular cloning and expression of a mouse thiamin pyrophosphokinase cDNA. J Biol Chem 1999; 274 (48) 34129-34133
- 4 Ortigoza-Escobar JD, Alfadhel M, Molero-Luis M. et al; Thiamine Deficiency Study Group. Thiamine deficiency in childhood with attention to genetic causes: survival and outcome predictors. Ann Neurol 2017; 82 (03) 317-330
- 5 Stefl S, Nishi H, Petukh M, Panchenko AR, Alexov E. Molecular mechanisms of disease-causing missense mutations. J Mol Biol 2013; 425 (21) 3919-3936
- 6 Invernizzi F, Panteghini C, Chiapparini L. et al. Thiamine-responsive disease due to mutation of tpk1: importance of avoiding misdiagnosis. Neurology 2017; 89 (08) 870-871
- 7 Zhu L, Wu R, Ye Z. et al. Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing. J Pediatr Endocrinol Metab 2019; 32 (03) 295-300
- 8 Fraser JL, Vanderver A, Yang S. et al. Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies. Mol Genet Metab Rep 2014; 1: 66-70
- 9 Vlasova TI, Stratton SL, Wells AM, Mock NI, Mock DM. Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood. J Nutr 2005; 135 (01) 42-47
- 10 Huang W, Qin J, Liu D. et al. Reduced thiamine binding is a novel mechanism for TPK deficiency disorder. Mol Genet Genomics 2019; 294 (02) 409-416