Objective: To describe the clinical manifestation of a patient with TPK1 mutation.

Background: A number of defects in thiamine metabolism are reported to cause various childhood onset acute encephalopathy, lactic acidosis, dystonia and psychomotor retardation. TPK1 mutations resulting in thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) is the most recently described disorder in this group. Twelve other TPK1 mutated patients have been reported so far, but severe dyskinesia has not been reported.

Method: Case report.

Results: A 40-year-old woman had childhood onset generalized dystonia and severe dyskinesia was referred to our clinic for consideration of deep brain stimulation. She was the forth child born at term after an uneventful pregnancy from non-consanguineous parents. She had an episode of Leigh-like encephalopathy with lactic acidosis at the age of 3, when she had tremor and unsteady gait. At 6 years, she had left foot focal dystonia. At 12 years, the dystonia spread to her whole body. In addition, she started to have disabling generalized jerky involuntary movements. Her younger sister presented similarly at the age of 7 years with severe dystonia but she had no involuntary movements. The patient underwent genetic testing, which revealed one heterozygous pathogenic variant (c.502-1G>T, transcript NM_022445.3) and one heterozygous variant of uncertain significance (c.167C>T, transcript NM_022445.3) in TPK1 gene.

Conclusion: TPK1 mutation can cause a broad range of clinical symptoms and severity. As more cases are diagnosed, the clinical and molecular spectrum of TPK1 mutation continues to expand. Apart from dystonia, severe dyskinesia can also be a prominent feature during the disease course.

References: 1. Mayr JA et al. Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway. Am J Hum Genet. 2011 Dec 9;89(6):806-12. 2. Banka S et al. Expanding theclinical and molecular spectrum of thiamine pyrophosphokinase deficiency: a treatable neurological disorder caused by TPK1 mutations. Mol Genet Metab. 2014 Dec;113(4):301-6. 3. Fraser JL 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 Feb 11;1:66-70. 4. Invernizzi F et al. Thiamine-responsive disease due to mutation of tpk1: Importance of avoiding misdiagnosis. Neurology. 2017 Aug 22;89(8):870-871. 5. Mahajan A et al. TPK1 mutation induced childhood onset idiopathic generalized dystonia: Report of a rare mutation and effect of deep brain stimulation. J Neurol Sci. 2017 May 15;376:42-43.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tpk1-mutation-induced-childhood-onset-dystonia-and-dyskinesia/