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DOI: 10.1055/s-0032-1307080
Acetazolamide as treatment for GLUT1 deficiency syndrome?
Introduction:
GLUT1-deficiency syndrome (OMIM #606 777) is a rare autosomal dominant disorder which may be associated with symptoms such as developmental delay, epilepsy or movement disorders. Movement disorders can present as paroxysmal or exercise-induced dyskinesias (Leen et al, 2010; Schneider et al, 2009). Similar movement disorders are found in episodic ataxia type 2. The movement disorders are caused by altered membrane excitability due to a defect of voltage-gated calcium channels. Treatment of episodic ataxia type 2 is acetazolamide, the classic therapy in GLUT1 deficiency syndrome consists in ketogenic diet.
Case report:
We report on a 23-month-old patient with paroxysmal ataxia, abnormal eye movements, dysarthria, dystrophy, microcephaly and developmental delay. Based on the clinical diagnosis of episodic ataxia type 2, treatment with acetazolamide was initiated. Subsequently a significant improvement of cognitive performance and ataxia was observed. The further diagnostic work-up revealed a decreased CSF-serum glucose ratio (0.37). This finding was confirmed by genetic testing, by which a pathogenic mutation of the SLC2A1 gene was found. Because of the diagnosis of a GLUT1-deficiency-syndrome initiation of ketogenic diet was planned. The dosage of acetazolamide was reduced. Afterwards there was a marked deterioration of clinical symptoms. After the dosage was increased to the prior level the symptoms improved again. This therapeutic effect could be reproduced even under controlled conditions.
Discussion:
Therapy with acetazolamide showed a significant improvement of ataxia and cognitive performance. This effect could be reproduced under control after temporarily stopping the medication. This observation is in accordance with a case report in the literature (Anheim et al. 2011). The exact mechanisms are not conclusively explained yet. Patients with a disappointing response to ketogenic diet or with compliance problems could benefit from a therapeutic trial with acetazolamide.