SLC19A3related

SLC19A3-related disorders refer to a spectrum of neurological diseases caused by biallelic pathogenic variants in the SLC19A3 gene, which encodes thiamine transporter 2 (THTR2). Thiamine transport is essential for cerebral energy metabolism, and impairment can disrupt neuronal function, particularly in the basal ganglia.

Clinical features commonly begin in infancy or early childhood with episodes of acute or subacute encephalopathy, hypotonia, dystonia or other movement abnormalities, ataxia, and feeding difficulties. Seizures can occur, and patients may experience developmental regression during episodes. Neuroimaging typically reveals symmetric involvement of the basal ganglia, especially the caudate nucleus and putamen, sometimes with additional white matter changes.

Genetically, these conditions are inherited in an autosomal recessive pattern. Affected individuals have pathogenic variants in both copies of SLC19A3, though the specific variants can vary. The condition has been described under the umbrella of biotin-thiamine-responsive basal ganglia disease (BTBGD), reflecting the notable responsiveness to treatment.

Diagnosis is suggested by the combination of clinical presentation and characteristic MRI findings and is confirmed by genetic testing identifying biallelic SLC19A3 variants. Additional metabolic and enzymatic studies may be performed to exclude other causes of encephalopathy; differential diagnosis includes other metabolic, infectious, and neurodegenerative disorders.

Management centers on prompt treatment with high-dose biotin and thiamine, which can lead to marked clinical improvement, particularly when initiated early during episodes. Long-term prognosis varies; many patients stabilize or improve with therapy, though some may have persistent neurologic deficits despite treatment. Regular follow-up and supportive care are important components of management.