[MIM 606 370]

(Episodic encephalopathy due to a dysfunction of thiamine metabolism type 5)

See also TRMA and Thiamine Metabolism Dysfunction.

Very rare. Autosomal recessive transmission of a mutation of the TPK1 gene (7q35) coding for thiamine pyrophosphokinase. This cytoplasmic enzyme catalyzes the transformation of thiamine into thiamine pyrophosphate which is transported into the mitochondria to act as a  cofactor of transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase in glycolysis and the ATP production of ATP..

Clinical presentation: episodes of encephalopathy related to infection or a  metabolic problem resulting in progressive neurological degradation similar to late onset Leigh disease with walking disorders, ataxia, dystonia and spasticity that can result in loss of walking. There are gradually lesions of the basal ganglia at MRI. During acute episodes, there is an increase in blood and CSF lactates levels, as well as an increase in urinary α-ketoglutarate.

Diagnosis: very low blood levels of thiamine pyrophosphate.

Treatment: dietary supplements of thiamine 100-200mg/day have little effect in symptomatic patients. Early treatment with higher doses  (500 mg/day) could be more effective. 

Anesthetic implications:

management of a mitochondrial cytopathy

References :

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Updated: May 2021