GLUT1 eksikliği sendromunda fenotipik spektrum ve tanısal evrim: tek merkezli yetişkin kohort deneyimi

Özet (abstract)

Abstract Background Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare neurometabolic disorder caused by pathogenic variants in the SLC2A1 gene. It is classically described as an infantile-onset condition; however, an expanding phenotypic spectrum is increasingly recognised, including diagnoses in adulthood. In this retrospective review of an adult cohort with GLUT1-DS, we explore the phenotypic diversity and diagnostic evolution within this cohort. Methods This retrospective case series was a single-centre study conducted at one metabolic centre and included adult patients with confirmed clinical, biochemical or genetic GLUT1-DS. Results Thirty-one individuals were identified with a median age of 27 years (IQR: 22–37). Median age at symptom onset was 3 years (IQR: 0–7). Median diagnostic delay was 6.5 years (IQR: 0.75–27.25) with a maximal delay of 47 years. 56% of individuals were diagnosed via genetic testing, most commonly by targeted single gene sequencing, with a shift towards exome and whole genome sequencing (WGS) in more recent cases. Individuals with a mixed phenotype (seizure and movement disorder) had the lowest median diagnostic delay (3.5 years, IQR: 1–13). The longest diagnostic delay was seen in movement-disorder predominant phenotypes (10 years, IQR: 2.5–37). Loss-of-function SLC2A1 variants tended to present earlier and with seizure-predominant or mixed phenotypes, whereas missense variants more commonly presented later with movement disorder-predominant phenotypes. Conclusion This case series demonstrates the marked phenotypic heterogeneity in GLUT1-DS. It also charts the evolution in diagnostic methods over the last few decades, illustrating how the increased availability of WGS and cascade testing has identified milder and atypical phenotypes. Widespread adoption of cascade testing would help identify individuals with undiagnosed GLUT1-DS and further define the full spectrum of GLUT1 deficiency.

Yazarların özeti; kaynağından alınmıştır. Orphanet Journal of Rare Diseases, 2026 · DOI ↗