Case Report: Atypical hepatobiliary manifestations associated with erythrocyte membrane instability in glucose...

Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1DS) is a rare neurometabolic disorder caused by pathogenic variants in SLC2A1. While neurological symptoms such as early-onset epilepsy, developmental delay, and movement disorders are well documented, hematologic and hepatobiliary complications are rarely reported, and their underlying mechanisms remain poorly defined.

We report a boy diagnosed with GLUT1DS at five years of age who presented with intractable seizures and persistent indirect hyperbilirubinemia. Genetic testing identified a heterozygous in-frame deletion in SLC2A1 [c.1306_1308del (p.Ile436del)], confirming the diagnosis of GLUT1DS. A co-occurring heterozygous UGT1A1 variants including coding and promoter lesions were also identified, initially suggestive of impaired bilirubin conjugation. During follow-up, the patient developed recurrent episodes of jaundice, anemia, and abdominal pain, ultimately attributed to chronic hemolysis with gallstone-related cholestasis requiring endoscopic retrograde cholangiopancreatography. To assess erythrocyte membrane integrity, specialized red blood cell studies were performed at 11 years of age. A temperature-dependent potassium leak test demonstrated cold-enhanced cation leakage consistent with pseudohyperkalemia and cryohydrocytosis, providing functional evidence of erythrocyte membrane instability associated with GLUT1 dysfunction.

This case expands the phenotypic spectrum of GLUT1DS by linking erythrocyte membrane instability to recurrent hemolysis and rarely reported hepatobiliary complications. Functional evaluation of erythrocyte membrane integrity may facilitate recognition of atypical systemic manifestations of GLUT1DS and supports the need for multidisciplinary surveillance beyond neurological care.