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Licensed Unlicensed Requires Authentication Published by De Gruyter February 21, 2019

Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing

  • Lina Zhu , Ruijuan Wu , Zhenlong Ye , Ruijie Gu , Yongxia Wang , Yu Hou , Zhichun Feng and Xiuwei Ma EMAIL logo



The mutations of thiamine pyrophosphokinase-1 (TPK1) gene have been frequently studied in some patients with thiamine metabolism dysfunction syndrome-5 (THMD5), while TPK1 mutations in Chinese patients have been investigated by only homozygous. A search of the literature on the mutations in the Chinese population currently published revealed that no reports of compound heterozygous mutations were reported. Here, we report a Chinese patient with compound heterozygous TPK1 mutations who underwent magnetic resonance imaging (MRI), whole exome sequencing (WES), molecular diagnosis, bioinformatics analysis, and three-dimensional (3D) protein structure analysis.

Case presentation

A Chinese boy was born after an uneventful pregnancy to non-consanguineous and healthy parents. On the sixth day after his birth, the lactate level of the patient was between 8.6 mmol/L and 14.59 mmol/L in plasma (the normal level is in the range of 0.5–2.2 mmol/L). Lactate was reduced to the normal level after rehydration, acid correction, expansion, and other treatments. After 4 months, the patient presented with an acute, 3-h-long, non-induced convulsions, and was admitted to our hospital for weakness, decreased oral intake, and lethargy. Results achieved by electroencephalography (EEG), cerebrospinal fluid, and other biochemical findings were normal. A visible hemorrhagic lesion was also observed in the brain. Seizures increased significantly during infection, which was accompanied by higher lactic acid levels. MRI of the brain showed an obvious signal shadow, in which bilateral frontal and temporal parietal subarachnoid cavities were widened, and more abnormal signals were observed; therefore, further consideration of hypoxic-ischemic encephalopathy and genetic metabolic disease was taken into account.


The results of WES revealed that the patient was associated with compound heterozygous mutations NM_022445.3:c.[263G>A]; [226A>G] of TPK1. His parents were non-consanguineous; while his father was found to be a heterozygous carrier with the mutation c.[263G>A], his mother was identified as a heterozygous carrier with the mutation c.[226A>G]. The results indicated that the patient had a compound heterozygous TPK1 mutation, and this is the first reported case in China.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2018-09-06
Accepted: 2018-12-26
Published Online: 2019-02-21
Published in Print: 2019-03-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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