Table 1.

Genetic mutations affecting thiamine metabolism.

Name of disease	Mutation	Protein	Age at onset	Clinical symptoms	Management (dose) (reference)
TRMA/Rogers syndrome	SLC19A2	THTR1	Birth to adolescence	Megaloblastic anemia, diabetes mellitus, sensorineural deafness, optic atrophy, congenital heart defects, short stature	Thiamine (50–100 mg/day) (77)
Biotin–thiamine-responsive basal ganglia disease	SLC19A3	THTR2	Birth to adolescence	Episodic encephalopathy associated with febrile illness, seizures, external ophthalmoplegia, dysphagia, gait ataxia, bilateral lesions of the basal ganglia	– Biotin (5–10 mg/kg/day), thiamine (300–900 mg) (78) – Biotin (5–10 mg/kg/day), thiamine (100–200 mg) (79)
Amish lethal microcephaly/THMD3	SLC25A19	Mitochondrial TPP carrier	Birth	Episodic encephalopathy associated with lactic acidosis and alpha-ketoglutaric aciduria, microcephaly, delayed psychomotor development, seizures, increased urinary lactate	– Phenobarbital (for seizures) and physical therapy (80) – High-fat diet (81)
Thiamine metabolism dysfunction syndrome 4/THMD4 (progressive polyneuropathy type)	SLC25A19	MTPC	Adolescence	Episodic encephalopathy associated with febrile illness, transient neurologic dysfunction, residual weakness, progressive axonal polyneuropathy, bilateral striatal degeneration	High-dose thiamine administered at the time of the study. Outcome not available (82)
Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) THMD5	TPK1	Thiamine phosphokinase 1	Early childhood	Episodic encephalopathy (Leigh-like) associated with high serum and CSF lactate with progressive neurologic and motor dysfunctions (gait disturbances, ataxia, dystonia, and spasticity, which, in some cases, may result in loss of ability to walk) triggered by infections. Cognitive function usually preserved; some developmental delay. Some patients may recover from some neurologic deficits; in others, the outcome is fatal.	Oral thiamine (100–200; 500 mg/day) (83, 84)