RESUMO
We hypothesized that children receiving medium-chain triglyceride ketogenic diet (MCTKD) experience similar seizure reduction despite lower ketosis compared with classic ketogenic diet (CKD). Children initiating CKD or MCTKD were enrolled in a prospective observational study. Forty-five children completed 6 months of KD (n = 17 MCTKD, n = 28 CKD). The proportion achieving ≥50% seizure reduction was 71% CKD group and 59% MCTKD group; ≥90% reduction was 32% and 36% in CKD and MCTKD groups, respectively. CKD had higher urine ketones (≥8 mmol/L: 79% vs. 36%, p = 0.005). Children receiving MCTKD experience similar seizure control to CKD despite lower urine ketone measures.
Assuntos
Dieta Cetogênica , Cetose , Insuficiência Renal Crônica , Criança , Feminino , Humanos , Masculino , Convulsões , Resultado do Tratamento , TriglicerídeosRESUMO
BACKGROUND: Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood-brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. We report on the phenotypic spectrum of patients with pediatric GLUT1DS as well as their diagnostic methods from a single center in Canada. METHODS: We reviewed patient charts for clinical features, biochemical and molecular genetic investigations, neuroimaging, treatment modalities, and outcomes of patients with GLUT1DS at our institution. RESULTS: There were 13 patients. The most common initial symptom was seizures, with the most common seizure type being absence seizures (85%). Seventy-seven percent of the patients had movement disorders, and dystonia and ataxia were the most common movement disorders. Fifty-four percent of the patients did not have a history of developmental delay during their initial presentation, whereas all patients had developmental delay, intellectual disability, or cognitive dysfunction during their follow-up. All patients had a pathogenic or likely pathogenic variant in SLC2A1 and missense variants were the most common variant type. CONCLUSION: We present 13 patients with GLUT1DS in the pediatric patient population. Atypical clinical features such as hemiplegia and hemiplegic migraine were present in an infant; there was a high prevalence of absence seizures and movement disorders in our patient population. We report an increased number of patients with GLUT1DS since the introduction of next-generation sequencing in the clinical settings. We believe that GLUT1DS should be included in the differential diagnosis of seizures, movement disorders, and hemiplegic migraine.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos , Dieta Cetogênica , Transportador de Glucose Tipo 1/metabolismo , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Dieta Cetogênica/métodos , Proteínas Facilitadoras de Transporte de Glucose , Transportador de Glucose Tipo 1/genética , Humanos , Lactente , Proteínas de Transporte de Monossacarídeos/genética , Convulsões/genéticaRESUMO
Between July of 2012 and December of 2014, 39 patients were enrolled prospectively to investigate the prevalence of glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None of them had GLUT1 deficiency. All patients seen in the same clinic within the same period were reviewed retrospectively. A total of 18 of these 85 patients had a genetic diagnosis, including GLUT1 deficiency, pathogenic copy number variants, congenital disorder of glycosylation, neuronal ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis, lissencephaly, and SCN1A-, SCN8A-, and STXBP1-associated epileptic encephalopathies. The prevalence of genetic diagnoses was 21% and prevalence of GLUT1 deficiency was 2.4% in our retrospective cohort study.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/complicações , Erros Inatos do Metabolismo dos Carboidratos/genética , Dieta Cetogênica/métodos , Epilepsia/complicações , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Erros Inatos do Metabolismo dos Carboidratos/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/dietoterapia , Epilepsia/epidemiologia , Epilepsia/genética , Feminino , Humanos , Masculino , Proteínas de Transporte de Monossacarídeos/genética , PrevalênciaRESUMO
OBJECTIVE: Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield in epileptic encephalopathy, we performed a retrospective cohort study in a single epilepsy genetics clinic. METHODS: We included all patients with intractable epilepsy, global developmental delay, and cognitive dysfunction seen between January 2012 and June 2014 in the Epilepsy Genetics Clinic. Electronic patient charts were reviewed for clinical features, neuroimaging, biochemical investigations, and molecular genetic investigations including targeted next-generation sequencing of epileptic encephalopathy genes. RESULTS: Genetic causes were identified in 28% of the 110 patients: 7% had inherited metabolic disorders including pyridoxine dependent epilepsy caused by ALDH7A1 mutation, Menkes disease, pyridox(am)ine-5-phosphate oxidase deficiency, cobalamin G deficiency, methylenetetrahydrofolate reductase deficiency, glucose transporter 1 deficiency, glycine encephalopathy, and pyruvate dehydrogenase complex deficiency; 21% had other genetic causes including genetic syndromes, pathogenic copy number variants on array comparative genomic hybridization, and epileptic encephalopathy related to mutations in the SCN1A, SCN2A, SCN8A, KCNQ2, STXBP1, PCDH19, and SLC9A6 genes. Forty-five percent of patients obtained a genetic diagnosis by targeted next-generation sequencing epileptic encephalopathy panels. It is notable that 4.5% of patients had a treatable inherited metabolic disease. SIGNIFICANCE: To the best of our knowledge, this is the first study to combine inherited metabolic disorders and other genetic causes of epileptic encephalopathy. Targeted next-generation sequencing panels increased the genetic diagnostic yield from <10% to >25% in patients with epileptic encephalopathy.
Assuntos
Predisposição Genética para Doença , Mutação/genética , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Adolescente , Caderinas , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Transtornos Cognitivos/genética , Estudos de Coortes , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Canal de Potássio KCNQ2 , Masculino , Proteínas Munc18 , Canal de Sódio Disparado por Voltagem NAV1.2 , Protocaderinas , Trocadores de Sódio-Hidrogênio , Espasmos Infantis/complicaçõesRESUMO
OBJECTIVES: The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy. METHODS: A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed. RESULTS: One hundred two children met inclusion criteria and were followed on the diet for up to 24 months. Thirteen of 102 (13%) children were neutropenic at diet initiation. In the remaining 89 children, 27 developed neutropenia. Developing neutropenia was significantly associated with the ketogenic diet at 6 (13%), 12 (23%), and 24 (25%) months follow-up. Developing neutropenia was associated with higher urinary ketones (OR = 4.26, 95% CI: 1.27, 14.15) and longer duration of ketogenic diet therapy (OR = 3.29, 95% CI: 1.42, 7.96). There was no significant association between development of a clinically significant infection and neutropenia. CONCLUSION: Ketogenic diet therapy is associated with neutropenia in children with epilepsy, however, it does not have a significant clinical impact. Concern regarding neutropenia should not discourage the use of the ketogenic diet in children.
Assuntos
Dieta Cetogênica/efeitos adversos , Epilepsia/dietoterapia , Neutropenia/epidemiologia , Fatores Etários , Criança , Epilepsia/urina , Feminino , Humanos , Cetonas/urina , Masculino , Neutropenia/diagnóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To identify underlying genetic causes in patients with pediatric movement disorders by genetic investigations. METHODS: All patients with a movement disorder seen in a single Pediatric Genetic Movement Disorder Clinic were included in this retrospective cohort study. We reviewed electronic patient charts for clinical, neuroimaging, biochemical, and molecular genetic features. DNA samples were used for targeted direct sequencing, targeted next-generation sequencing, or whole exome sequencing. RESULTS: There were 51 patients in the Pediatric Genetic Movement Disorder Clinic. Twenty-five patients had dystonia, 27 patients had ataxia, 7 patients had chorea-athetosis, 8 patients had tremor, and 7 patients had hyperkinetic movements. A genetic diagnosis was confirmed in 26 patients, including in 20 patients with ataxia and 6 patients with dystonia. Targeted next-generation sequencing panels confirmed a genetic diagnosis in 9 patients, and whole exome sequencing identified a genetic diagnosis in 14 patients. CONCLUSIONS: We report a genetic diagnosis in 26 (51%) patients with pediatric movement disorders seen in a single Pediatric Genetic Movement Disorder Clinic. A genetic diagnosis provided either disease-specific treatment or effected management in 10 patients with a genetic diagnosis, highlighting the importance of early and specific diagnosis.
RESUMO
Williams-Beuren syndrome is rarely associated with epilepsy. One previously reported case showed an association with apnoeic seizures while a few other cases showed an association with infantile epileptic spasms and generalized and focal seizures. We report the case of a 13-month-old boy with a deletion typically associated with Williams-Beuren syndrome, who presented with isolated apnoeic seizures which were refractory to multiple antiepileptic drugs but partially responsive to the ketogenic diet. The diagnosis was challenging due to a complex cardiac history, gastroesophageal reflux, and normal interictal EEG findings. This case highlights the importance of prolonged EEG monitoring in suspected cases of apnoeic seizures. Further, given the reported cases of unexplained sudden death in Williams-Beuren syndrome, this case raises the possibility of an association between apnoeic seizures and unexplained sudden death. [Published with video sequence on www.epilepticdisorders.com].
Assuntos
Epilepsia Resistente a Medicamentos/genética , Convulsões/genética , Encéfalo/fisiopatologia , Diagnóstico Diferencial , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/dietoterapia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia , Humanos , Lactente , Masculino , Convulsões/diagnóstico , Convulsões/dietoterapia , Convulsões/fisiopatologia , Deleção de Sequência , Síndrome de Williams/diagnóstico , Síndrome de Williams/genéticaRESUMO
Defects in adenosine deaminase enzyme cause severe immunodeficiency. Without enzyme replacement or allogeneic bone marrow transplantation, patients often suffer fatal infection in infancy. Adenosine deaminase is expressed ubiquitously; deficiency may affect various organs, including the brain. Neurologic abnormalities occur in some adenosine deaminase-deficient patients, mostly in association with infection or after bone marrow transplantation. Three cases with significant neurologic abnormalities, including hypotonia, head lag, nystagmus, difficulty in focusing gaze, seizure disorder, and moderate-severe developmental delay but with no evidence of infection or transplant-related medication toxicity are presented. Computed tomographic scans and cranial MRI revealed volume loss and abnormalities of basal ganglia and thalamus, which may reflect accelerated nerve cell death or altered stimulation of adenosine receptors. Detailed neurologic and neuroimaging evaluation should be performed for all patients with adenosine deaminase deficiency upon diagnosis, to identify potentially significant brain lesions.
Assuntos
Adenosina Desaminase/deficiência , Doenças do Sistema Nervoso/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/etiologia , Deficiências do Desenvolvimento/patologia , Humanos , Lactente , Masculino , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/patologia , RadiografiaRESUMO
BACKGROUND: Severe intellectual disability has been reported in a subgroup of patients with Duchenne muscular dystrophy but is not typically associated with Becker muscular dystrophy. PATIENT: The authors report a 13-year-old boy, with severe intellectual disability (Wechsler Intelligence Scales for Children-IV, Full Scale IQ < 0.1 percentile), attention-deficit hyperactivity disorder, and mild muscle weakness. He had elevated serum creatine kinase and dystrophic changes on muscle biopsy. Dystrophin immunohistochemistry revealed decreased staining with the C-terminal and mid-rod antibodies and essentially absent staining of the N-terminal immunostain. Sequencing of muscle mRNA revealed aberrant splicing due to a c.10797+5G > A mutation in DMD. CONCLUSION: Dystrophinopathy may be associated with predominantly cognitive impairment and neurobehavioral disorder, and should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males.
Assuntos
Distrofina/genética , Deficiência Intelectual/genética , Distrofia Muscular de Duchenne/genética , Adolescente , Humanos , Masculino , MutaçãoRESUMO
Anti-glutamic acid decarboxylase directed antibodies are a rare cause of autoimmune limbic encephalitis that is relatively resistant to immunotherapy. Here we report a 15-year-old boy with nonparaneoplastic, anti-glutamic acid decarboxylase limbic encephalitis presenting with subacute headache, memory disturbance, psychiatric symptoms, and seizures. At onset, his memory disturbance manifested as transient global amnesia-like episodes. Clinical remission was achieved with rituximab, intravenous immunoglobulin, and corticosteroids.
Assuntos
Anticorpos/sangue , Doenças Autoimunes/sangue , Glutamato Descarboxilase/imunologia , Encefalite Límbica/sangue , Adolescente , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Eletroencefalografia , Humanos , Encefalite Límbica/imunologia , Encefalite Límbica/fisiopatologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
The very-high-fat ketogenic diet can worsen lipid levels in children with pre-existing hyperlipidemia by increasing serum lipoproteins and reducing antiatherogenic high-density lipoproteins. A retrospective chart review of 160 children treated with the ketogenic diet from September 2000 to May 2011 was performed. Twelve children with pre-existing hyperlipidemia were identified. Lipid levels including total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and total cholesterol/high-density lipoprotein were measured pre-diet and at 3, 6, and 12 months of treatment. During treatment, there was a significant reduction in mean total cholesterol, low-density lipoprotein, and total cholesterol/high-density lipoprotein. Total cholesterol and low-density lipoprotein were normalized in 8 and 7 children at 6 months; and 9 and 9 children at 12 months respectively. At 6 and 12 months, tot cholesterol/HDL ratio was normalized in 5 and 7 children respectively. Diet modifications were made to achieve healthy lipid levels. By extrapolating the data, it suggests lipid levels can be controlled in children and adults with ketogenic diet treatment.
Assuntos
Anticonvulsivantes/uso terapêutico , Dieta Cetogênica/métodos , Epilepsia/dietoterapia , Hiperlipidemias , Metabolismo dos Lipídeos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Epilepsia/complicações , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/dietoterapia , Hiperlipidemias/metabolismo , Lactente , Masculino , Estudos Retrospectivos , Fatores de TempoAssuntos
Anemia/sangue , Cobre/deficiência , Síndrome de Lennox-Gastaut/dietoterapia , Neutropenia/sangue , Anemia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Criança , Cobre/sangue , Cobre/farmacologia , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/dietoterapia , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia , Feminino , Humanos , Síndrome de Lennox-Gastaut/tratamento farmacológico , Neutropenia/tratamento farmacológicoRESUMO
Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The authors describe a 9-year-old girl who needed concentrations twice the normal amount to control recurrent episodes of decreased levels of consciousness. Except for nystagmus, she had no other signs of phenytoin toxicity. This patient highlights the critical principle in therapeutic drug monitoring of individualizing drug therapy. Although some patients receiving phenytoin may achieve seizure control with "subtherapeutic" levels (i.e., <40 micromol/L), others may need supratherapeutic levels, as was the case with this patient. Clinicians should be careful not to treat "numbers" (i.e., serum concentrations), but rather the patient's clinical condition, with a careful balance between therapeutic advantage and adverse effects.