Intermittent Alternating Eye-Head Synkinesia in GLUT1 Deficiency Syndrome

Background

Glucose is the main energy source of the brain and crosses the blood-brain barrier through glucose transporter proteins [1]. Within the main glucose transporter families, glucose transporter 1 (GLUT1) and its corresponding gene SLC2A were identified in 1985 [2]. De Vivo et al. first described two cases of GLUT1 deficiency syndrome (GLUT1-DS) in 1991 [3]. The classic phenotype is characterized by seizures, developmental delay, microcephaly, and a variable degree of spasticity [3]. The nonclassical phenotype (15 – 20%) includes a huge spectrum of manifestations and is potentially lethal at a very early age [4]. Oculomotor involvement is described in both phenotypes and includes eye rolling, horizontal roving eye movements, and head bobbing [1]. A retrospective case series from Pearson et at., which looked at 101 patients with GLUT1-DS in the United States, found a documented history of paroxysmal abnormal eye movements in 32% of the patients with GLUT1-DS, with episodes preceding the onset of seizures in 63% of them [5]. To date, about 100 children worldwide are known to suffer from GLUT1-DS, classified as a rare disease (OMIM 606 777). In our case, the isolated unusual eye and head movements led to an initial ophthalmological referral and it is our goal with this report to raise awareness of this rare and treatable condition in the ophthalmological community.

Publication History

Received: 09 September 2020

Accepted: 17 November 2020

Article published online:
19 February 2021

• References

• 1 Brockmann K. The expanding phenotype of Glut 1-deficiency syndrome. Brain Dev 2009; 31: 545-552
• 2 Mueckler M, Caruso C, Baldwin SA. et al. Sequence and structure of a human glucose transporter. Science 1985; 229: 941-945
• 3 Anand G, Padeniya A, Hanrahan D. et al. Milder phenotypes of glucose transporter type 1 deficiency syndrome. Dev Med Child Neurol 2011; 53: 664-668
• 4 Wang D, Pascual JM, Yang H. et al. Glut1 deficiency syndrome: clinical, genetic and therapeutic aspects. Ann Neurol 2005; 57: 111-118
• 5 Pearson TS, Pons R, Engelstad K. et al. Paroxysmal eye–head movements in Glut1 deficiency syndrome. Neurology 2017; 88: 1666-1673
• 6 Graef S, Irwin MS, Wan MJ. Incidence and Prognostic Role of the Ocular Manifestations of Neuroblastoma in Children. Am J Ophthalmol 2020; 213: 145-152
• 7 Klepper J, Voit T. Facilitated glucose transporter protein type 1 (Glut 1) deficiency syndrome: impaired glucose transporter into brain – a review. Eur J Pediatr 2002; 161: 295-304
• 8 Klepper J, Garcia-Alvarez M, OʼDriscoll KR. et al. Erythrocyte 3-O-methyl-D-glucose uptake essay for diagnosis of glucose-transporter-protein syndrome. J Clin Lab Anal 1999; 13: 116-121
• 9 Sourbron J, Klinkenberg S, van Kuijk SMJ. et al. Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. Childs Nerv Syst 2020; 36: 1099-1109
• 10 Ho YY, Yang H, Klepper J. et al. Glucose transporter type 1 deficiency syndrome (Glut1DS): methylxanthines potentiate GLUT1 haploinsufficiency in vitro . Pediatr Res 2001; 50: 254-260