Excellent response to acetazolamide in a case of paroxysmal dyskinesias due to GLUT1-deficiency

Abstract

Heterozygous mutations in the SLC2A1 gene, which encodes glucose transport protein type 1 (GLUT1), are responsible for GLUT1 deficiency, leading to cerebral energy failure associated with low cerebrospinal fluid (CSF) glucose concentrations [3, 6]. Most patients have permanent or paroxysmal movement disorders, and paroxysmal exerciseinduced dyskinesias (PED) or paroxysmal non-kinesigenic dyskinesia (PNKD) is sometimes the main motor manifestation [3, 4, 6]. Acetazolamide can reduce the frequency and severity of paroxysmal episodes in episodic ataxia type 2 (EA2), but its effect on paroxysmal dyskinesia (PDysk) is controversial [1, 2, 4]. An 18-year-old girl was presented who had PDysk from the age of 2 years. She had healthy unrelated parents and no noteworthy family history. Her birth measurements were normal (including head circumference: 34 cm; 50th percentile) She had been a clumsy child with poor balance. Her condition had started to deteriorate at age 16 years with PDysk episodes of increasing severity and frequency of up to three episodes weekly, each lasting from 5 to 10 min. The PDysk were precipitated by sustained physical exercise, fasting, caffeine, tiredness, heat and stress. At age 18 years, examination showed mild cerebellar signs, microcephaly (3rd percentile) and mental retardation (IQ = 63). Magnetic resonance imaging of the brain was normal. EA2 and spinocerebellar ataxia type 6 were excluded by CACNA1A gene analysis. Laboratory findings were normal apart from mild hypoglycorrhachia (40 mg/dL) and a low CSF-to-blood glucose ratio (0.50, N [ 0.59). Molecular studies identified a missense mutation (p.Ser294Pro) in the