RESUMO
Null.
Assuntos
Hiperglicinemia não Cetótica , Humanos , Hiperglicinemia não Cetótica/complicações , Hiperglicinemia não Cetótica/diagnósticoRESUMO
A 5-year-old boy presented with subacute motor regression since age 2.5 years. Examination revealed spasticity of bilateral lower extremities, generalized dystonia, and pseudobulbar palsy. Investigations revealed raised plasma lactate (2.5 mmol/L, normal range 0.8-1.5 mmol/L) and no evidence of sideroblastic anemia. Neuroimaging showed cavitating leukoencephalopathy with involvement of long tracts (corticospinal, spinothalamic tracts) and dorsolateral columns of cervicothoracic cord (Figures 1 and 2). A next-generation sequencing test identified a novel homozygous missense variant (c.171C > A, p.Phe57Leu) in exon 1 of the Glutaredoxin-5 (GLRX5) gene.
Assuntos
Hiperglicinemia não Cetótica , Masculino , Humanos , Pré-Escolar , Hiperglicinemia não Cetótica/complicações , Hiperglicinemia não Cetótica/diagnóstico por imagem , Hiperglicinemia não Cetótica/genética , Glutarredoxinas/genética , Mutação de Sentido Incorreto , Homozigoto , ÉxonsRESUMO
BACKGROUND: Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. CASE: The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. CONCLUSION: Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.
Assuntos
Anticonvulsivantes/administração & dosagem , Dieta Cetogênica , Hiperglicinemia não Cetótica/terapia , Nitrilas/administração & dosagem , Piridonas/administração & dosagem , Humanos , Hiperglicinemia não Cetótica/complicações , Lactente , Masculino , Convulsões/complicações , Convulsões/tratamento farmacológico , Resultado do TratamentoAssuntos
Coreia , Hiperglicinemia não Cetótica/complicações , Idoso , Idoso de 80 Anos ou mais , Coreia/diagnóstico por imagem , Diabetes Mellitus/terapia , Dislipidemias/terapia , Feminino , Hemoglobinas Glicadas , Humanos , Hipertensão/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Nonketotic hyperglycinemia is a rare inborn error of glycine metabolism characterized by a severe metabolic encephalopathy with drug-resistant seizures. Here, we report the outcome of nonketotic hyperglycinemia in a cohort of patients diagnosed and followed-up at a tertiary care reference center in Lebanon, between 2000 and 2014.Eight out of 12 patients with nonketotic hyperglycinemia were retrospectively reviewed. The remainders were excluded for incomplete data. The majority of cases presented with seizures and hypsarrhythmia or burst suppression patterns. Half of the patients died. Survival varied between 7 days and 18 years. Seizures remained unresponsive with poor outcome, despite standard supportive care and antiepileptic therapy; however, two patients were responsive to ketogenic diet and one of them became seizure-free.Scarce data on the outcome of nonketotic hyperglycinemia patients from the Middle East and North Africa region are available. The ketogenic diet, in combination with standard therapies, appears to be effective in controlling the seizures in this devastating disorder. Larger multicenter studies are still needed to establish the role of the ketogenic diet in nonketotic hyperglycinemia.
Assuntos
Dieta Cetogênica , Hiperglicinemia não Cetótica/dietoterapia , Convulsões/dietoterapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hiperglicinemia não Cetótica/complicações , Hiperglicinemia não Cetótica/mortalidade , Lactente , Recém-Nascido , Líbano , Masculino , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
O diabetes e suas complicações constituem as principais causas de mortalidade precoce na maioria dos países. O envelhecimento da população e a crescente prevalência da obesidade e do sedentarismo, além dos processos de urbanização, são considerados os principais fatores responsáveis pelo aumento da incidência e da prevalência do diabetes mellitus (DM) em todo o mundo. Este relato de caso objetiva descrever a presença de distúrbio do movimento em idoso por conta do estado hiperosmolar não cetótico. A combinação de hemicoreia-hemibalismo, hiperglicemia não cetótica e envolvimento dos gânglios da base em exames de imagem é considerada uma síndrome única. Os distúrbios do movimento em estado hiperosmolar não cetótico apresentam resposta terapêutica satisfatória com o uso de neurolépticos e controle glicêmico adequado. A escassez de trabalhos publicados proporciona subdiagnósticos clínico e laboratorial, interferindo no prognóstico e no acompanhamento dos pacientes.
Diabetes mellitus (DM) and its complications constitute the leading causes of early mortality in most countries. Population aging and the growing prevalence of obesity and sedentary lifestyles, in addition to spreading urbanization, are considered the main drivers of the increasing incidence and prevalence of DM worldwide. This case report describes the acute onset of movement disorder in an older woman secondary to hyperosmolar hyperglycemic state (HHS). The combination of hemichoreahemiballismus, HHS, and evidence of basal ganglia involvement on neuroimaging is considered a unique syndrome. Movement disorders secondary to HHS respond satisfactorily to administration of neuroleptic agents and proper glycemic control. The lack of published studies on this pathologic entity may lead to clinical and laboratory underdiagnosis, with negative impacts on patient prognosis and follow-up.
Assuntos
Humanos , Feminino , Idoso , Coreia/tratamento farmacológico , Coreia/diagnóstico por imagem , Hiperglicinemia não Cetótica/complicações , Discinesias/tratamento farmacológico , Discinesias/diagnóstico por imagem , Complicações do Diabetes , Psicotrópicos/uso terapêutico , Diabetes Mellitus/fisiopatologia , Hipoglicemiantes , Transtornos dos Movimentos/diagnósticoAssuntos
Diabetes Mellitus Tipo 2/complicações , Discinesias , Hidralazina/administração & dosagem , Hipertensão/complicações , Insulina/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Adesão à Medicação , Putamen/diagnóstico por imagem , Anti-Hipertensivos/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Discinesias/diagnóstico , Discinesias/tratamento farmacológico , Discinesias/etiologia , Discinesias/fisiopatologia , Humanos , Hiperglicinemia não Cetótica/sangue , Hiperglicinemia não Cetótica/complicações , Hipertensão/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Nonketotic Hyperglycinemia is an autosomal recessive disorder characterized by defects in the mitochondrial glycine cleavage system. Most patients present soon after birth with seizures and hypotonia, and infants that survive the newborn period often have profound intellectual disability and intractable seizures. Here we present a case report of a 4-year-old girl with NKH as well as hyperammonemia, an uncommon finding in NKH. Genetic analysis found a previously unreported homozygous mutation (c.878-1 G > A) in the AMT gene. Maximum Entropy Principle modeling predicted that this mutation most likely breaks the splice site at the border of intron 7 and exon 8 of the AMT gene. Treatment with L-Arginine significantly reduced both the proband's glycine and ammonia levels, in turn aiding in control of seizures and mental status. This is the first time the use of L-Arginine is reported to successfully treat elevated glycine levels.
Assuntos
Aminometiltransferase/genética , Hiperamonemia/genética , Hiperglicinemia não Cetótica/genética , Íntrons , Mutação , Pré-Escolar , Feminino , Homozigoto , Humanos , Hiperamonemia/complicações , Hiperglicinemia não Cetótica/complicaçõesRESUMO
Nonketotic hyperglycinemia (NKH) is a devastating inborn error of glycine metabolism caused by deficient activity of the glycine cleavage enzyme. Classically, patients present with lethargy, hypotonia, myoclonic jerks, transient respiratory depression in the first week of life and often progress to death. Surviving infants have profound psychomotor retardation, refractory epilepsy and poor quality of life. Currently, no effective therapeutic avenues exist for severe NKH. Ketogenic diet (KD) has been trialled only in a small group of patients with neonatal NKH and early myoclonic encephalopathy, in whom significant improvements in seizure control were reported. We describe an infant with classical neonatal NKH who presented on the third day of life with hypotonia, poor feeding, respiratory insufficiency resulting in ventilatory support and seizures with burst-suppression pattern on electroencephalogram (EEG). KD initiated at age 6 months for intractable seizures, lead to a dramatic decrease in seizure frequency, EEG improvements, normalisation of plasma glycine levels, reduced spasticity and improved quality of life. KD may be a valuable treatment modality for refractory seizure control in classical NKH.
Assuntos
Dieta Cetogênica/métodos , Epilepsia/dietoterapia , Hiperglicinemia não Cetótica/dietoterapia , Epilepsia/congênito , Humanos , Hiperglicinemia não Cetótica/complicações , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Nonketotic hyperglycinemia (NKH) is an autosomal recessive severe life-threatening catostrophic metabolic disorder. MATERIALS AND METHODS: The present study was conducted in a tertiary reference center in Turkey for six years period. The accurate diagnosis of six NKH patients was based on clinical history of the patients, neurological examinations, seizure semiology, serial electroencephalography (EEG) recordings, neuroimaging findings, metabolic tests and genetic analysis. RESULTS: The common clinical findings were hypotonia with severe head lag, poor feeding, poor sucking, and intractable seizures. The starting age of the symptoms was between birth and 45â¯days of age (median: 8â¯days). The starting age of the seizures was between 30â¯min of age and 45â¯days of age (median: 18â¯days). The age of accurate diagnosis was between 1â¯month of age and 5.5â¯months of age (mean: 3.75⯱â¯1.69â¯months). The cerebrospinal fluid (CSF) to plasma GLY ratio of the patients was between 0.031 and 0.21 (median: 0.16). The EEG patterns of the patients were suppression-burst, hypsarrhythmia, multifocal epileptic activity, and right centro-occipital epileptic activity on admission. The neuroimaging findings were diffuse hypomyelination, corpus callosum (CC) hypoplasia, CC agenesis and brainstem hypoplasia on the magnetic resonance imaging and glycine peak was evidenced on magnetic resonance spectroscopy. Four of the patients were mutation-positive. CONCLUSIONS: If a child is encephalopathic and/or hypotonic with severe head lag, early evaluation of the EEG records should be made even without a history of clinical seizures. The disease has a heterogenous course and the clinical outcome depends on the mutation type.
Assuntos
Hiperglicinemia não Cetótica/diagnóstico , Hipotonia Muscular/diagnóstico , Convulsões/diagnóstico , Idade de Início , Eletroencefalografia , Feminino , Humanos , Hiperglicinemia não Cetótica/complicações , Hiperglicinemia não Cetótica/patologia , Hiperglicinemia não Cetótica/fisiopatologia , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Hipotonia Muscular/etiologia , Mutação , Convulsões/etiologia , Convulsões/patologia , Convulsões/fisiopatologia , TurquiaRESUMO
A neonate presented with early encephalopathy deteriorated and was intubated and ventilated. Ventilator data were monitored and recorded at 100 Hz for 24 hours.The infant had many sudden deep inspirations during this time which were initially thought to be seizures. These were characterised by short, rapid, large inspirations when the airway pressure was reduced well below the positive end expiratory pressure level. Analysis of the ventilator data showed that these were hiccupping episodes misinterpreted by the ventilator as spontaneous breaths and triggering ventilator inflations. The expired tidal volumes during the hiccupping episodes were more than double the set 4.5 mL/kg. During these episodes, there was no change in the level of consciousness or in the amplitude-integrated electroencephalogram signal. Detailed respiratory recording of pathological hiccups has not been reported.Metabolic screening diagnosed non-ketotic hyperglycinaemia. Hiccups commonly occur in this condition and should not be misinterpreted as seizures, spontaneous breaths or gasps.
Assuntos
Hiperglicinemia não Cetótica/diagnóstico , Encefalopatias/etiologia , Diagnóstico Diferencial , Evolução Fatal , Soluço/etiologia , Humanos , Hiperglicinemia não Cetótica/complicações , Hiperglicinemia não Cetótica/terapia , Recém-Nascido , Masculino , Respiração ArtificialRESUMO
An 85-year-old man with a history of diabetes was admitted with acute onset hemichorea. Laboratory findings confirmed poorly controlled diabetes. A brain computed tomography (CTC) revealed contralateral striatal hyperdensity. The findings were compatible with hyperglycaemia-induced hemichorea, and antidiabetic and symptomatic treatment was initiated. The symptoms remitted completely after six days, and a follow-up CTC showed partial resolution of the striatal changes. This case illustrates the importance of considering if hyperglycaemia is the cause of hemichorea, as early diagnosis and treatment yield an excellent prognosis.
Assuntos
Coreia/etiologia , Hiperglicinemia não Cetótica/complicações , Idoso de 80 Anos ou mais , Coreia/diagnóstico , Coreia/diagnóstico por imagem , Coreia/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Hiperglicinemia não Cetótica/diagnóstico , Hiperglicinemia não Cetótica/diagnóstico por imagem , Hiperglicinemia não Cetótica/tratamento farmacológico , Masculino , Acidente Vascular Cerebral/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Historically, d-glyceric aciduria was thought to cause an uncharacterized blockage to the glycine cleavage enzyme system (GCS) causing nonketotic hyperglycinemia (NKH) as a secondary phenomenon. This inference was reached based on the clinical and biochemical results from the first d-glyceric aciduria patient reported in 1974. Along with elevated glyceric acid excretion, this patient exhibited severe neurological symptoms of myoclonic epilepsy and absent development, and had elevated glycine levels and decreased glycine cleavage system enzyme activity. Mutations in the GLYCTK gene (encoding d-glycerate kinase) causing glyceric aciduria were previously noted. Since glycine changes were not observed in almost all of the subsequently reported cases of d-glyceric aciduria, this theory of NKH as a secondary syndrome of d-glyceric aciduria was revisited in this work. We showed that this historic patient harbored a homozygous missense mutation in AMT c.350C>T, p.Ser117Leu, and enzymatic assay of the expressed mutation confirmed the pathogeneity of the p.Ser117Leu mutation. We conclude that the original d-glyceric aciduria patient also had classic NKH and that this co-occurrence of two inborn errors of metabolism explains the original presentation. We conclude that no evidence remains that d-glyceric aciduria would cause NKH.
Assuntos
Ácidos Glicéricos/urina , Hiperglicinemia não Cetótica/complicações , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/genética , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Aminometiltransferase/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diagnóstico Diferencial , Epilepsia , Ácidos Glicéricos/metabolismo , Glicina/metabolismo , Homozigoto , Humanos , Hiperglicinemia não Cetótica/diagnóstico , Hiperglicinemia não Cetótica/etiologia , Hiperglicinemia não Cetótica/genética , Hiperoxalúria Primária/diagnóstico , Masculino , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Mutação de Sentido Incorreto , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Transferases/genética , Transferases/metabolismoRESUMO
Epilepsia partialis continua is a rare epileptic syndrome observed in patients with brain structural lesions and metabolic disorders. We report a patient with non-ketotic hyperglycaemia presenting as epilepsia partialis continua with reversible focal brain lesions. An 83-year-old woman visited our hospital due to sudden and repetitive left facial twitching lasting for two days. Initial laboratory data revealed serum glucose, osmolality, and sodium levels of 631 mg/dl, 310 mOsm/l, and 130 mEq/l, respectively. EEG was normal. Brain MRI showed low signal changes in the right frontal subcortical area and high signal changes in the surrounding right frontal cortical areas on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. No seizures recurred after correcting blood glucose levels, hydrating the patient, and infusing valproate (900 mg/day). Follow-up MRI, six months later, showed complete resolution of the signal changes in the right frontal cortical and subcortical areas and no clinical seizures. When considering non-ketotic hyperglycaemia with epilepsia partialis continua in an elderly patient, early diagnosis and administration of the appropriate therapy is very important in order to decrease morbidity.
Assuntos
Encéfalo/diagnóstico por imagem , Epilepsia Parcial Contínua/etiologia , Hiperglicinemia não Cetótica/complicações , Idoso de 80 Anos ou mais , Eletroencefalografia , Epilepsia Parcial Contínua/diagnóstico por imagem , Feminino , Humanos , Hiperglicinemia não Cetótica/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Early myoclonic encephalopathy (EME) presents in neonatal period with erratic or fragmentary myoclonus and a burst-suppression electroencephalography (EEG) pattern. Nonketotic hyperglycinemia (NKH) is the most common metabolic cause of EME and genetic testing confirms the diagnosis of NKH in around 75% of the patients with a clinical diagnosis of NKH. Three genes are known to cause NKH. Here we describe a case of EME caused by NKH in which a new mutation in aminomethyltransferase (AMT) gene has been detected.
Assuntos
Aminometiltransferase/genética , Hiperglicinemia não Cetótica/genética , Espasmos Infantis/genética , Eletroencefalografia , Humanos , Hiperglicinemia não Cetótica/complicações , Recém-Nascido , Masculino , MutaçãoRESUMO
Nonketotic hyperglycemia has been described as a metabolic cause of Hemiballism-hemichorea (HB-HC), especially in elderly patients with poorly controlled diabetes. Pathophysiology is not known yet. MRI features tend to be hyperintense in the putamen on T1-weighted images. We present conventional MRI with diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI) features of two cases with nonketotic hyperglycemia. T1 hyperintensity without diffusion restriction on DWI and minimal putaminal hypointensity without phase shift on SWI were compatible with either pathological mineralization or petechial microhemorrhage or protein denaturation. In the type 2 diabetic patients with HC-HB, conventional MRI together with SWI and DWI will guide to clinician to plan treatment approach.