GLUT1 deficiency syndrome in clinical practice
Introduction
In 1991 GLUT1 deficiency syndrome (GLUTDS) was first described as an early-onset childhood epileptic encephalopathy caused by impaired glucose transport across the blood–brain barrier and into brain cells (De Vivo et al., 1991). Defects in the facilitated glucose transporter GLUT1 resulted in low CSF glucose levels termed hypoglycorrhachia. The majority of patients carry mutations in the SLC2A1 gene encoding the GLUT1 transporter. To date close to 200 patients have been identified worldwide (Klepper and Leiendecker, 2007, Rotstein and De Vivo, 2010). The classical phenotype of an early-onset epileptic encephalopathy rapidly expanded. To date the complex clinical phenotype includes an epileptic encephalopathy with complex movement disorders in variable combinations, paroxysmal events, specific seizure types, and adult manifestations. The low glucose concentration in the cerebrospinal fluid (CSF) termed hypoglycorrhachia represents the biochemical hallmark of the disease and thus the diagnostic gold standard. This gold standard has been challenged by an increasing number of clinical subtypes with moderate if all hypoglycorrhachia who clinically and genetically clearly carry a definite diagnosis of GLUT1DS. Also, the spectrum of SLC2A1-mutations has rapidly expanded with several hot spots arising (Klepper and Leiendecker, 2007, Leen et al., 2010). However, patients sharing identical mutations often do not have identical clinical manifestations indicating that there are additional mechanisms such as modifying genes and proteins that alter phenotype and potentially contribute to the pathophysiology of this complex entity (Nickels and Wirrell, 2010).
Within the setting of an increasing complexity of symptoms, mutations, and therapeutic regimens, diagnosing and treating GLUT1DS has become a challenge. Here we outline the clinical practice of GLUT1DS in view of the current literature.
Section snippets
Suspecting GLUT1DS
There is a classical manifestation of GLUT1DS: intractable epilepsy within the first six months of life followed by global developmental delay and a complex movement disorder (Klepper and Leiendecker, 2007, Leen et al., 2010). Symptoms may increase on fasting and improve on carbohydrate intake reflecting the cerebral energy deficit – in fact an adult patient was served honey at bedside in the morning by his wife to improve his alertness and neurological functioning (Brockmann et al., 2001).
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