Absence of Mutation in the SLC2A1 Gene in a Cohort of Patients with Alternating Hemiplegia of Childhood (AHC)
ABSTRACT Alternating hemiplegia of childhood (AHC) is a rare neuropediatric disorder classically characterized by episodes of hemiplegia developing in the first months of life, various non-epileptic paroxysmal events and global neurological impairment. If the etiology is unresolved, the disorder is highly suspected to be monogenic with DE NOVO autosomal dominant mutations. A missense mutation in the SLC2A1 gene encoding the facilitative glucose transporter-1 (GLUT1) was recently described in a child fulfilling the existing criteria for the diagnosis of AHC, with the exception of age at onset, thus suggesting a clinical overlap between AHC and GLUT1 deficiency syndrome due to SLC2A1 mutations. We have studied a cohort of 23 patients to investigate whether patients with classical AHC harbor SLC2A1 mutations. Automated Sanger sequencing and MLPA analyses failed to detect any SLC2A1 mutations in the 23 patients analyzed, thus excluding mutations of this gene as a frequent cause of classical AHC.
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ABSTRACT: A syndrome of alternating hemiplegia of childhood (AHC) is a rare disorder first presented in 1971. AHC is characterized by transient episodes of hemiplegia affecting either one or both sides of the body. Age of onset is before 18 months and the common earliest manifestations are dystonic or tonic attacks and nystagmus. Hemiplegic episodes last minutes to days and the frequency and duration tend to decrease with time. Motor and intellectual development is affected, deficits may also develop later. Epileptic seizures occur in some patients. Neuroimaging of the brain usually reveals no abnormalities. The variability of individual clinical presentations and evolution of symptoms have made diagnosis difficult. Therefore the problems of misdiagnosis could account for the low prevalence of this syndrome. This paper hopes to present actual data on AHC, especially of the results of genetic research and new diagnostic tools.Neurologia i neurochirurgia polska 03/2014; 48(2):130-135. DOI:10.1016/j.pjnns.2013.05.003 · 0.54 Impact Factor
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ABSTRACT: Alternating hemiplegia of childhood is a rare, predominantly sporadic disorder. Diagnosis is clinical, and little is known about genetics. Glucose transporter 1 deficiency syndrome shares with alternating hemiplegia of childhood paroxysmal and nonparoxysmal symptoms. The aim of the study was to investigate glucose transporter 1 mutations in 30 Italian patients. Genetic material was analyzed by DNA amplification and glucose transporter 1 region sequencing. Mutational analysis findings of the SLC2A1 gene were negative in all patients. The pattern of movement disorders was reviewed. Interictal dystonia and multiple paroxysmal events were typical of alternating hemiplegia of childhood. In conclusion, alternating hemiplegia of childhood is a heterogeneous clinical condition, and although glucose transporter 1 deficiency can represent an undiagnosed cause of this disorder, mutational analysis is not routinely recommended. Alternatively, a careful clinical analysis and the 3-O-methyl-D-glucose uptake test can allow prompt identification of a subgroup of patients with alternating hemiplegia of childhood treatable with a ketogenic diet.Journal of child neurology 08/2012; 28(7). DOI:10.1177/0883073812452789 · 1.67 Impact Factor
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ABSTRACT: Alternating hemiplegia of childhood (AHC) is a rare disease characterized by an early onset of hemiplegic episodes and other paroxysmal and permanent neurologic features. Recently, mutations in the ATP1A3 gene have been identified as the causal mechanism of AHC. Regarding the differential diagnosis of AHC, glucose transporter 1 deficiency syndrome may be considered because these two disorders share some paroxystic and nonparoxystic features. We report a typical case of AHC harboring a de novo mutation in the ATP1A3 gene, together with a duplication and insertion in the SLC2A1 gene who exhibited marked clinical improvement following ketogenic diet. Because the contribution of the SLC2A1 mutation to the clinical phenotype cannot be definitely demonstrated, the remarkable clinical response after ketogenic diet led us to the hypothesis that ketogenic diet might be effective in AHC as it provides an alternative energy source for the brain.Pediatric Neurology 12/2013; 50(4). DOI:10.1016/j.pediatrneurol.2013.11.017 · 1.50 Impact Factor