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Eur J Med Genet. 2015 Sep;58(9):443-54. doi: 10.1016/j.ejmg.2015.06.007. Epub 2015 Jul 17.

From splitting GLUT1 deficiency syndromes to overlapping phenotypes.

Author information

1
AP-HP, Necker-Enfants Malades Hospital, Department of Pediatric Neurology, Paris, France. Electronic address: marie.hully@nck.aphp.fr.
2
AP-HP, Bichat Hospital, Biochemistry and Genetic Laboratory, Paris, France.
3
AP-HP, Necker-Enfants Malades Hospital, Department of Pediatric Radiology, Paris, France.
4
AP-HP, Necker-Enfants Malades Hospital, Department of Neurophysiology, Paris, France.
5
Evelina London Children's, Hospital Children's Neurosciences Centre, Block D, First Floor, SouthWing, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, United Kingdom.
6
AP-HP, Necker-Enfants Malades Hospital, Department of Pediatric Metabolic Disorders, Paris, France.
7
University Hospital of Toulouse, Children Hospital, Department of Pediatric Neurology, Toulouse, France.
8
University Hospital of Lyon, Department of Pediatric Neurology, Lyon, France.
9
University Hospital of Montpellier, Department of Pediatric Neurology, Montpellier, France.
10
AP-HP, Trousseau Hospital, Department of Pediatric Neurology, Paris, France.
11
Hospital of St-Brieuc, Department of Pediatrics, St-Brieuc, France.
12
AP-HP, Pitié-Salpêtrière Hospital, Department of Neurology, Paris, France.
13
University Hospital of Strasbourg, Department of Pediatric Neurology, Strasbourg, France.
14
University Hospital of Strasbourg, Department of Medical Genetics, Strasbourg, France.
15
Pellegrin Hospital, University Hospital of Bordeaux, Department of Pediatric Neurology, Bordeaux, France.
16
University Hospital of Rouen, Department of Medical Genetics, Rouen, France.
17
University Hospital of Rouen, Department of Neonatology and Pediatric Reanimation, Rouen, France.
18
University Hospital of Rouen, Metabolic Biochemistry Department, Rouen, France.
19
Pays d'Aix Hospital, Department of Pediatrics, Aix en Provence, France.
20
University Hospital of Nantes, Pediatric Intensive Care Unit, Nantes, France.
21
University Hospital of Poitiers, Department of Pediatrics, Poitiers, France.
22
AP-HP, Necker-Enfants Malades Hospital, Department of Pediatric Neurology, Paris, France.

Abstract

INTRODUCTION:

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder due to mutations or deletions in SLC2A1, resulting in impaired glucose uptake through the blood brain barrier. The classic phenotype includes pharmacoresistant epilepsy, intellectual deficiency, microcephaly and complex movement disorders, with hypoglycorrhachia, but milder phenotypes have been described (carbohydrate-responsive phenotype, dystonia and ataxia without epilepsy, paroxysmal exertion-induced dystonia). The aim of our study was to provide a comprehensive overview of GLUT1DS in a French cohort.

METHODS:

265 patients were referred to the French national laboratory for molecular screening between July 2006 and January 2012. Mutations in SLC2A1 were detected in 58 patients, with detailed clinical data available in 24, including clinical features with a focus on their epileptic pattern and electroencephalographic findings, biochemical findings and neuroimaging findings.

RESULTS:

53 point mutations and 5 deletions in SLC2A1 were identified. Most patients (87.5%) exhibited classic phenotype with intellectual deficiency (41.7%), epilepsy (75%) or movement disorder (29%) as initial symptoms at a medium age of 7.5 months, but diagnostic was delayed in most cases (median age at diagnostic 8 years 5 months). Sensitivity to fasting or exertion in combination with those 3 main symptoms were the main differences between mutated and negative patients (p < 0.001). Patients with myoclonic seizures (52%) evolved with more severe intellectual deficiency and movement disorders compared with those with Early Onset Absence Epilepsy (38%). Three patients evolved from a classic phenotype during early childhood to a movement disorder predominant phenotype at a late childhood/adulthood.

CONCLUSIONS:

Our data confirm that the classic phenotype is the most frequent in GLUT1DS. Myoclonic seizures are a distinctive feature of severe forms. However a great variability among patients and overlapping through life from milder classic phenotype to paroxysmal-prominent- movement-disorder phenotype are possible, thus making it difficult to identify definite genotype-phenotype correlations.

KEYWORDS:

Child; Epilepsy; Genotype; Glut1 deficiency syndrome (GLUT1DS); Outcome; Phenotype

PMID:
26193382
DOI:
10.1016/j.ejmg.2015.06.007
[Indexed for MEDLINE]

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