Thiamine metabolism dysfunction syndrome type IV without encephalopathy: an atypical presentation

Abstract

Background Thiamine metabolism dysfunction syndrome type-4 (THMD-4) is an exceptionally rare autosomal recessive neuro-metabolic disorder characterized by febrile illness-associated episodic encephalopathy, bilateral striatal necrosis, and progressive polyneuropathy. It is caused by bi-allelic pathogenic variations in the SLC25A19 gene encoding the mitochondrial thiamine pyrophosphate carrier. THMD-4 typically presents with recurrent episodes of encephalopathy and weakness triggered by febrile illness, posing diagnostic challenges due to its rarity and variable clinical manifestations. Case Presentation : We report the case of an 8-year-old boy, developmentally normal, presenting with weakness in all four limbs following a febrile episode. Notably, the patient lacked altered sensorium. Clinical examination revealed distal muscle weakness, abnormal gait, and absent deep tendon reflexes. Neuroimaging demonstrated characteristic bilateral basal ganglia lesions. Genetic testing identified bi-allelic pathogenic variants in SLC25A19, confirming the diagnosis of THMD-4. Treatment with high-dose biotin and thiamine resulted in gradual improvement of weakness. Conclusion This case highlights an unusual presentation of THMD-4 characterized by the absence of typical encephalopathic features. Despite the atypical clinical manifestation, characteristic imaging findings and genetic testing enabled definitive diagnosis. Early recognition of diverse presentations of THMD-4 is crucial for timely intervention and prevention of neurological sequelae. Increased awareness among clinicians about the variable clinical spectrum of THMD-4 can facilitate prompt diagnosis and optimize patient outcomes.