Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018991 (hemiplegia)
 3,997 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Absence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC). 2144 18

Glucose transporter type 1 deficiency syndrome is characterized by infantile onset seizures, development delay, movement disorders, and acquired microcephaly. The phenotype includes allelic variants such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia of childhood with or without epilepsy. Dystonias involve allelic variants of glucose transporter type 1 deficiency syndrome. Three Chinese patients presented with paroxysmal behavioral disturbance, weakness, ataxia (especially after fasting), and exercise intolerance. Electroencephalogram findings did not correlate with clinical manifestations. Cranial magnetic resonance imaging produced normal results or mild hypomyelination. Hypoglycorrhachia was evident in all cases. Cerebrospinal fluid glucose ranged from 1.63-2.45 mmol/L. Erythrocyte 3-O-methyl-d-glucose uptake was decreased to 58% in patient 1. Three SLC2A1 disease-causing mutations (761delA, P383H, and R400C) were observed. No patient tolerated ketogenic diets. Two patients responded to frequent meals with snacks. Cerebrospinal fluid evaluation constitutes the diagnostic testing permitting early treatment of glucose transporter type 1 deficiency syndrome. Early diagnosis and treatment improve prognoses.
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PMID:Allelic variations of glut-1 deficiency syndrome: the chinese experience. 2270 13

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.
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PMID:Lack of SLC2A1 (glucose transporter 1) mutations in 30 Italian patients with alternating hemiplegia of childhood. 2289 93

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is the result of impaired glucose transport into the brain. The "classic" GLUT1DS patient presents with infantile seizures (resistant to traditional seizure medications), developmental delay, acquired microcephaly, hypotonia, spasticity, and a complex movement disorder consisting of ataxia and dystonia. However, over the years, other clinical manifestations have been described, such as paroxysmal exertion-induced dystonia with or without seizures, choreoathetosis, alternating hemiplegia, and other paroxysmal events, such as intermittent ataxia, dystonia, and migraine. At the current state of the art in understanding of GLUT1DS, classifying the disease phenotype as "classical" or "non-classical" seems to be of limited clinical utility. It seems more appropriate to think in terms of a broad clinical spectrum in which we can observe intellectual impairment, acquired microcephaly, epilepsy, and movement disorders characterized by different clinical manifestations and degrees of severity. Lumbar puncture, a simple investigation, should be considered the first diagnostic step that, moreover, is feasible worldwide. Thereafter, mutational analysis of the solute carrier family 2 (facilitated glucose transporter) member 1 (SLC2A1) gene should be performed in patients with highly suggestive clinical findings and low cerebrospinal fluid glucose (<50mg/dl or ratio <0.60). Early diagnosis is critical because it allows prompt initiation of treatment with a ketogenic diet (KD). Childhood is the critical period for treatment of GLUT1DS: early diagnosis is crucial for an effective etiological therapy. KD treatment can be useful in adulthood too. Compliance has been found to be much better in GLUT1DS than in the other conditions for which KD treatment is indicated.
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PMID:GLUT1 deficiency syndrome 2013: current state of the art. 2389 Aug 38

The facilitative glucose transporter-1 (GLUT1) deficiency or de Vivo syndrome is a rare neuropediatric disorder characterized by drug-resistant epilepsy, acquired microcephaly, delayed psychomotor development, intermittent ataxia, and other paroxysmal neurological disorders due to the presence of dominant mutations in the SLC2A1 gene. Alternating hemiplegia of childhood (AHC) is another rare neuropediatric disorder characterized by episodes of hemiplegia developing during the first 1.5 years of life. Before the recent finding of the gene ATP1A3 as the major cause of AHC, a heterozygous missense mutation in the SLC2A1 gene encoding GLUT1 was described in one child with atypical AHC, suggesting some clinical overlap between AHC and GLUT1 deficiency syndrome (GLUT1DS1). Half of patients with symptoms evocative of GLUT1DS1 with hypoglycorrhachia and up to 25 % of patients with AHC remain molecularly undiagnosed. We investigated whether mutations in SLC2A3 encoding GLUT3, another glucose transporter predominant in the neuronal cell, may account the case of a cohort of 75 SLC2A1 negative GLUTDS1-like patients and seven patients with AHC who were negative for ATP1A3 and SLC2A1 mutations. Automated Sanger sequencing and qPCR analyses failed to detect any mutation of SLC2A3 in the patients analyzed, excluding this gene as frequently mutated in patients with GLUT1DS1 like or AHC.
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PMID:No Mutation in the SLC2A3 Gene in Cohorts of GLUT1 Deficiency Syndrome-Like Patients Negative for SLC2A1 and in Patients with AHC Negative for ATP1A3. 2400 17

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder featuring attacks of hemiplegia and other paroxysmal and non-paroxysmal manifestations leading to progressive neurological impairment. De novo mutations in ATP1A3 have been identified in up to 80% of patients. AHC is also associated with rare mutations in other genes involved in episodic neurological disorders. We sought to find mutations in ATP1A3, CACNA1A, ATP1A2, SCN1A and SLC2A1 in a cohort of ten unrelated patients from Spain and Greece. All patients fulfilled AHC diagnostic criteria. All five genes were amplified by PCR and Sanger sequenced. Copy number variation (CNV) analysis of SLC2A1 and CACNA1A was performed using two different approaches. We identified three previously described heterozygous missense ATP1A3 mutations (p.Asp801Asn, p.Glu815Lys and p.Gly947Arg) in five patients. No disease-causing mutations were found in the remaining genes. All mutations occurred de novo; carriers presented on average earlier than non-carriers. Intellectual disability was more severe with the p.Glu815Lys variant. A p.Gly947Arg carrier harbored a maternally-inherited CACNA1A p.Ala454Thr variant. Of note, three of our patients exhibited remarkable clinical responses to the ketogenic diet. We confirmed ATP1A3 mutations in half of our patients. Further AHC genetic studies will need to investigate large rearrangements in ATP1A3 or consider greater genetic heterogeneity than previously suspected.
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PMID:Clinical and genetic analysis in alternating hemiplegia of childhood: ten new patients from Southern Europe. 2499 92