Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndrome A Systematic Review
Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.JAMA neurology 09/2013; 70(11). DOI: 10.1001/jamaneurol.2013.3090
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.
- [Show abstract] [Hide abstract]
ABSTRACT: GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Besides the classic phenotype of intellectual disability, epilepsy, and movement disorders, other phenotypes are increasingly recognized. These include, for example, idiopathic generalized epilepsy and paroxysmal exercise-induced dyskinesia. Since the disorder has only been recognized for two decades and is mostly diagnosed in children, little is known about the disease course. Our purpose was to investigate the disease course of GLUT1DS patients with the classic, complex phenotype from infancy into adulthood. We performed a systematic literature review as well as a cohort study, including GLUT1DS patients aged 18 years and older. The literature search yielded a total of 91 adult GLUT1DS patients, of which 33 patients (one-third) had a complex phenotype. The cohort study included seven GLUT1DS patients with a complex phenotype who were prospectively followed up in our clinic from childhood into adulthood. Our results show that epilepsy is a prominent feature during childhood in classic GLUT1DS patients. During adolescence, however, epilepsy diminishes or even disappears, but new paroxysmal movement disorders, especially paroxysmal exercise-induced dyskinesia, either appear or worsen if already present in childhood. Intellectual disability was not systematically assessed, but cognitive functions appeared to be stabile throughout life. Like children, adolescents may benefit from a ketogenic diet or variants thereof.Journal of Neurology 01/2014; 261(3). DOI:10.1007/s00415-014-7240-z · 3.38 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The normal adult brain constitutes approximately 2% of the body weight and consumes approximately 20% of glucose in the body (about 120 g of glucose per day). In the nervous system, the aerobic metabolism of glucose is the main source of energy in the form of adenosine triphosphate (ATP); most of this energy is utilized to sustain excitatory synaptic transmission. The interaction among neurons, astrocytes, and endothelial cells has a central role coupling energy supply with changes in neuronal activity. These cells express different subtypes of glucose transporters (GLUTs) that mediate the sodium-independent facilitated transport of glucose across membranes. GLUT1 and GLUT3 are expressed in the nervous system, GLUT1 in endothelial cells and astrocytes, and GLUT3 in neurons. Astrocytes take up glucose from the blood and metabolize it to lactate, which is then delivered to neurons. The relative contribution of this astrocyte-to-neuron lactate shuttle as a main source of energy to sustain neuronal physiology, compared to direct glucose uptake by neurons, is a matter of debate; nevertheless, the role of GLUT1 in astrocytes is underscored by the range of clinical phenotypes associated with GLUT1 deficiency. There are several reviews on the biochemistry and physiology of GLUTs, neurometabolic coupling between astrocytes and neurons, the clinical consequences of GLUT1 deficiency, and the involvement of GLUT1 in other neurologic disorders.(1-7.)Neurology 03/2014; 82(15). DOI:10.1212/WNL.0000000000000328 · 8.29 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Paroxysmal exercise-induced dyskinesia (PED) is characterized by recurrent episodes of involuntary movement disorders usually precipitated by sustained walking or running. Recently, mutations in the gene encoding for glucose transporter type 1 (GLUT-1) were described in a number of families with autosomal dominant PED. However, the underlying etiology of PED is quite heterogeneous. We describe a large series of patients presenting with PED. Of 16 patients, we reached a conclusive diagnosis for 11 (4 patients with GLUT-1 mutations, 4 patients with early Parkinson's disease, 2 with dopa-responsive dystonia, and one with a psychogenic/functional movement disorder). For the remaining 5 patients, the final diagnosis remained descriptive. Although certain clinical features might allow etiological distinction between cases, clinical examination alone is not always conclusive. Based on our series, we propose a diagnostic algorithm to aid the differential diagnosis of PED.04/2014; 1(1). DOI:10.1002/mdc3.12007
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.