Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
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Lina Zhu
Abstract
Background
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.
Conclusions
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.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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.
References
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©2019 Walter de Gruyter GmbH, Berlin/Boston
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- Case Reports
- Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
- A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8
- Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature
Articles in the same Issue
- Frontmatter
- Original Articles
- Improved adherence and growth outcomes with jet-delivered growth hormone
- Validation of the Greek version of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire
- Growth hormone deficiency in children with antenatal Bartter syndrome
- Physical growth and development characteristics of children with Williams syndrome aged 0–24 months in Zhejiang Province
- Adiposity and adipocytokines: the moderator role of cardiorespiratory fitness and pubertal stage in girls
- Serum omentin-1 levels in obese children
- A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing
- Typical characteristics of children with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency: a single-centre experience and review of the literature
- Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients
- The effect of therapy on plasma ghrelin and leptin levels, and appetite in children with iron deficiency anemia
- The effect of PKU diet on the maternal quality of life and social discrimination in relation to their educational status and place of living
- Evaluating the four most important salivary sex steroids during male puberty: testosterone best characterizes pubertal development
- Case Reports
- Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
- A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8
- Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature
