Thiamine-responsive encephalopathy

Thiamine-responsive encephalopathy, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD) or thiamine metabolism dysfunction syndrome 2 (THMD2), is a rare inherited neurometabolic disorder caused by mutations in the SLC19A3 gene, which encodes a thiamine transporter (hTHTR2). This condition primarily affects the central nervous system, particularly the basal ganglia, and can lead to episodes of subacute encephalopathy often triggered by febrile illness, trauma, or other stressors. Key clinical features include recurrent episodes of confusion, seizures, dystonia, external ophthalmoplegia, dysphagia, and progressive neurological deterioration. During acute crises, patients may develop severe encephalopathy that can progress to coma and death if untreated. Brain MRI characteristically shows bilateral necrosis of the basal ganglia (particularly the caudate nuclei and putamina), as well as involvement of the thalami, cerebral cortex, and brainstem structures. The age of onset is typically in childhood, though infantile and later-onset forms have been described. The hallmark of this condition is its responsiveness to high-dose biotin and thiamine supplementation, which can dramatically reverse acute neurological symptoms if administered early. Early diagnosis and prompt initiation of treatment are critical, as delayed treatment may result in permanent neurological damage including severe disability or death. Lifelong supplementation with biotin and thiamine is required to prevent recurrent episodes. Despite treatment, some patients may develop residual neurological deficits, particularly if diagnosis was delayed. The condition follows an autosomal recessive inheritance pattern and has been reported predominantly in consanguineous families, particularly in populations from the Middle East.

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