Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndrome A Systematic Review
ABSTRACT IMPORTANCE GLUT1 deficiency syndrome is a treatable neurometabolic disorder, characterized by a low concentration of glucose in cerebrospinal fluid (CSF) and a decreased CSF to blood glucose ratio. Reports of patients with apparently normal CSF glucose levels, however, have raised the question whether CSF analysis is a reliable screening tool for GLUT1 deficiency syndrome. OBJECTIVE To determine the value of CSF analysis in the workup of GLUT1 deficiency syndrome. EVIDENCE REVIEW PubMed was searched until July 2012 by using the terms glucose transporter 1 (GLUT-1) deficiency syndrome, glucose transporter defect, and SLC2A1-gene. Relevant references mentioned in the articles were also included. The CSF results of all patients with genetically proven GLUT1 deficiency syndrome described in literature were reevaluated. FINDINGS The levels of glucose in CSF, the CSF to blood glucose ratios, and the levels of lactate in CSF were reported for 147 (94%), 152 (97%), and 73 (46%) of 157 patients, respectively. The CSF glucose levels ranged from 16.2 to 50.5 mg/dL and were at or below the 10th percentile for all 147 patients. The CSF to blood glucose ratios ranged from 0.19 to 0.59 and were at or below the 10th percentile for 139 of 152 patients (91%), but they could be within the normal range as well. The CSF lactate levels ranged from 5.4 to 13.5 mg/dL and were at or below the 10th percentile for 59 of 73 patients (81%). A typical CSF profile for GLUT1 deficiency syndrome, which is defined as a CSF glucose level at or below the 10th percentile, a CSF to blood glucose ratio at or below the 25th percentile, and a CSF lactate level at or below the 10th percentile, was found in only 35 of 4099 CSF samples (0.9%) present in our CSF database of patients who received a diagnosis other than GLUT1 deficiency syndrome. CONCLUSIONS AND RELEVANCE We conclude that if age-specific reference values are applied, CSF glucose and lactate levels are adequate biomarkers in the diagnostic workup of GLUT1 deficiency syndrome. Future availability of whole-exome sequencing in clinical practice will make the existence of a reliable biomarker for GLUT1 deficiency syndrome even more important, in order to interpret genetic results and, even more importantly, not to miss SLC2A1-negative patients with GLUT1 deficiency syndrome.
SourceAvailable from: Sébastien Lebon[Show abstract] [Hide abstract]
ABSTRACT: GLUT1 deficiency (GLUT1D) has recently been identified as an important cause of generalized epilepsies in childhood. As it is a treatable condition, it is crucial to determine which patients should be investigated. We analyzed SLC2A1 for mutations in a group of 93 unrelated children with generalized epilepsies. Fasting lumbar puncture was performed following the identification of a mutation. We compared our results with a systematic review of 7 publications of series of patients with generalized epilepsies screened for SLC2A1 mutations. We found 2/93 (2.1%) patients with a SLC2A1 mutation. One, carrying a novel de novo deletion had epilepsy with myoclonic-atonic seizures (MAE), mild slowing of head growth, choreiform movements and developmental delay. The other, with a paternally inherited missense mutation, had childhood absence epilepsy with atypical EEG features and paroxysmal exercise-induced dyskinesia (PED) initially misdiagnosed as myoclonic seizures. Out of a total of 1110 screened patients with generalized epilepsies from 7 studies, 2.4% (29/1110) had GLUT1D. This rate was higher (5.6%) among 303 patients with early onset absence epilepsy (EOAE) from 4 studies. About 50% of GLUT1D patients had abnormal movements and 41% a family history of seizures, abnormal movements or both. GLUT1D is most likely to be found in MAE and in EOAE. The probability of finding GLUT1D in the classical idiopathic generalized epilepsies is very low. Pointers to GLUT1D include an increase in seizures before meals, cognitive impairment, or PED which can easily be overlooked. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 12/2014; 19(2). DOI:10.1016/j.ejpn.2014.11.009 · 1.93 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: GLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission.Seizure 01/2015; 24. DOI:10.1016/j.seizure.2014.11.009 · 2.06 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We conducted a nationwide survey of glucose transporter type-1 deficiency syndrome (GLUT-1DS) in Japan in order to clarify its incidence as well as clinical and laboratory information. A questionnaire to survey the number of genetically and clinically confirmed cases of GLUT-1DS was sent to 1018 board-certified pediatric neurologists, which resulted in 57 patients being reported. We obtained the clinical and laboratory data of 33 patients through a secondary questionnaire. The age of the 33 patients (male: 15, female: 18) at the time of the study ranged between 3 and 35years (mean: 13.5years). The age of these patients at the onset of initial neurological symptoms ranged between the neonatal period and 48months (mean: 9.4months). GLUT-1DS was diagnosed at a mean age of 8.4years (range: 1year to 33years). The initial symptom was convulsive seizures, which occurred in 15 cases, and was followed by abnormal eye movements in 7 cases and apneic or cyanotic attacks in 4 cases. The latter two symptoms most frequently occurred early in infancy. Thirty-two patients (97%) exhibited some type of epileptic seizure. Neurological findings revealed that most patients had muscle hypotonia, cerebellar ataxia, dystonia, and spastic paralysis. Mild to severe mental retardation was detected in all 33 cases. Furthermore, paroxysmal episodes of ataxia, dystonia/dyskinesia, and motor paralysis were described in approximately 1/3 of all patients. The factors that frequently aggravated these events were hunger, exercise, fever, and fatigue, in that order. The mean CSF/blood glucose ratio was 0.36 (0.28-0.48). Pathological mutations in the SLC2A1 gene were identified in 28 out of 32 cases (87.5%). The results described herein provided an insight into the early diagnosis of GLUT1-DS, including unexplained paroxysmal abnormal eye movements, apneic/cyanotic attacks, and convulsive seizures in infancy, as well as uncommon paroxysmal events (ataxia, atonia, and motor paralysis) in childhood. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.Brain and Development 12/2014; DOI:10.1016/j.braindev.2014.11.006 · 1.54 Impact Factor