Banka S et al. Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: A treatable neurological disorder caused by TPK1 mutations. Mol Genet Metab. 2014 Oct 5. [Epub ahead of print]
Thiamine pyrophosphokinase (TPK) deficiency causing episodic encephalopathy type thiamine metabolism dysfunction is the most recently discovered thiamine-responsive inborn error of metabolism, with only five patients previously described in the literature. Lactic acidosis and 2-ketoglutaric aciduria appear to be markers of this disorder, although they do not seem to have been present in all cases. Banka et al describe two new patients with TPK deficiency, of which one had a non-episodic Leigh syndrome-like neurological presentation, thus expanding the clinical spectrum of this disorder. Significantly, an attempt to introduce a ketogenic diet in this patient before the diagnosis was made (and therefore before thiamine supplementation was introduced) resulted in severe metabolic acidosis and irreversible neurodevelopmental regression. The authors also describe assays for TPK enzyme activity measurement and thiamine pyrophosphate quantification in frozen muscle and blood.
This study highlights the importance of considering this potentially treatable disorder in the differential diagnosis of episodic encephalopathy or non-episodic Leigh-like syndrome, particularly in the presence of 2-ketoglutaric aciduria. It should also be considered before a ketogenic diet is offered to a patient in the absence of a firm alternative diagnosis.