NEONATAL AND EARLY-INFANTILE BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE MIMICKING LEIGH SYNDROME: A CASE SERIES AND DIAGNOSTIC CLUES

Abstract

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD), caused by biallelic pathogenic variants in SLC19A3, is a rare autosomal recessive neurometabolic disorder that is potentially reversible with early treatment. Neonatal and early-infantile forms may closely mimic Leigh syndrome, causing diagnostic delay. Case presentation: We describe two children with early-onset BTBGD. Case 1 was a 23-day-old term female neonate from a third-degree consanguineous family with a previous unexplained infant death, who developed refractory seizures and central hypotonia. MRI showed extensive bilateral symmetrical lesions involving the basal ganglia, thalami, deep white matter and brainstem in a Leigh-like pattern. Whole-exome sequencing (WES) with copy-number analysis identified a homozygous contiguous SLC19A3 deletion. Case 2 was a 10-month-old male from a third-degree consanguineous family who had normal early development before developing excessive crying, dystonia, seizures and neuroregression. MRI demonstrated symmetrical basal ganglia and brainstem abnormalities with an elevated lactate peak on magnetic resonance spectroscopy (MRS). WES confirmed SLC19A3-related BTBGD. Outcome: Both children received high-dose biotin and thiamine with supportive therapy and showed stabilization or improvement of acute neurological deterioration, although residual neurological deficits persisted. Conclusion: Bilateral symmetrical basal ganglia and brainstem lesions in a neonate or infant with seizures, dystonia or neuroregression should prompt consideration of BTBGD, even when routine metabolic investigations are normal or only mildly abnormal. Empirical biotin and thiamine should be started promptly when the diagnosis is suspected rather than awaiting molecular confirmation.