(THMD, acronym for THiamine Metabolism Dysfunction)

Group of diseases grouped under the term Episodic Encephalopathies due to a dysfunction of the metabolism of thiamin, the genetic origin  of which is varied and the transmission, autosomal recessive.

Five different types:

• type 1 (THMD1) [MIM 249 270]: thiamin-responsive megaloblastic anemia (TRMA) (see this term), diabetes and deafness, due to a mutation of the SLC19A2 gene (1q23.3)
• type 2 (THMD2) [MIM 607 483]: involvement to the basal ganglia responding to biotin, due to a mutation of the SLC19A3 gene (2q36) coding for a carrier of thiamin; episodic encephalopathy often triggered by a febrile episode and presenting as confusion, convulsions, external ophthalmoplegia, dysphagia and sometimes coma. It responds in a few days time to high doses of biotin or thiamin
• type 3 (THMD3) [MIM 607 196]: Amish-type microcephaly, due to a mutation of the SLC25A19 gene (17q25); severe microcephaly from birth, severe delay in psychomotor development, brain malformations, and episodic encephalopathy with lactic acidosis and alpha-ketoglutaric aciduria
• type 4 (THMD4) [MIM 613 710]: bilateral necrosis of striate nuclei with progressive polyneuropathy, due to a mutation of the SLC25A19 gene (17q25); episodic encephalopathy during early infancy, often triggered by a febrile episode and causing transient neurological dysfunction. Most patients recover but some have residual muscle weakness and develop progressive axonal polyneuropathy. MRI during seizures shows lesions consistent with degeneration or necrosis of the striate nuclei.
• type 5 (THMD5) [MIM 614 458]: thiamine pyrophosphokinase deficiency or episodic encephalopathy due to a dysfunction of thiamine metabolism type 5 (see this term), due to a mutation of the TPK1 gene (7q35).

Anesthetic implications: 

management of a mitochondrial cytopathy (see this term)

References : 

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Updated: May 2021