RESUMEN
AMP-activated protein kinase (AMPK) regulates many different metabolic pathways in eukaryote cells including mitochondria biogenesis and energy homeostasis. Here we identify a patient with hypotonia, weakness, delayed milestones and neurological impairment since birth harbouring a novel homozygous mutation in the AMPK catalytic α-subunit 1, encoded by the PRKAA1 gene. The homozygous mutation p.S487L in isoform 1 present in the patient is in a cryptic residue for AMPK activity. In the present study, we performed the characterization of mitochondrial respiratory properties of the patient, in comparison to healthy controls, through the culture of skin fibroblasts in order to understand some of the cellular consequences of the PRKAA1 mutation. In these assays, mitochondrial respiratory complex I showed lower activity, which was followed by a decrement in the mtDNA copy number, which is a probable consequence of the lower expression of PGC-1α and PRKAA1 itself as measured in our quantitative PCRs experiments. Confirming the effect of the patient mutation in respiration, transfection of patient fibroblasts with wild type PRKAA1 partially restore complex I level. The preliminary clinic evaluations of the patient suggested a metabolic defect related to the mitochondrial respiratory function, therefore treatment with CoQ10 supplementation dose started four years ago and a clear improvement in motor skills and strength has been achieved with this treatment.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Fibroblastos , Homocigoto , Mitocondrias , Mutación Missense , Consumo de Oxígeno , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Sustitución de Aminoácidos , Preescolar , Complejo I de Transporte de Electrón/genética , Complejo I de Transporte de Electrón/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Masculino , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al. described the first two cases of spontaneous periodic hypothermia associated with agenesis of the corpus callosum. Recently, Dundar et al. reported a case of spontaneous periodic hypothermia and hyperhidrosis without corpus callosum agenesis, suggesting that the periodic episodes of hypothermia might be of epileptiform origin. Here we describe two paediatric patients with spontaneous periodic hypothermia without corpus callosum agenesis and demonstrate, to our knowledge for the first time, altered levels of neurotransmitter metabolites within the cerebrospinal fluid.
Asunto(s)
Corteza Cerebral , Hiperhidrosis/complicaciones , Hipotermia/complicaciones , Neurotransmisores/metabolismo , Periodicidad , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Preescolar , Femenino , Humanos , LactanteRESUMEN
BACKGROUND: Ataxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD). CASES: We report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene. LITERATURE REVIEW: ATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity. CONCLUSIONS: In this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.
RESUMEN
Manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. This letter highlights the neurological manifestations and neuroimaging features of inherited manganism (IMn), an unusual and treatable inborn error of Mn homeostasis. Early-onset dystonia with "cock-walk" gait and hyperintense signal in basal ganglia, associated to polycythemia, chronic liver disease and hypermanganesemia, promptly suggest IMn, and a genetic evaluation should be performed.
Asunto(s)
Trastornos Neurológicos de la Marcha , Intoxicación por Manganeso , Neuroimagen , Proteínas de Transporte de Catión/genética , Niño , Femenino , Trastornos Neurológicos de la Marcha/complicaciones , Trastornos Neurológicos de la Marcha/genética , Trastornos Neurológicos de la Marcha/patología , Humanos , Intoxicación por Manganeso/complicaciones , Intoxicación por Manganeso/genética , Intoxicación por Manganeso/patología , Transportador 8 de ZincAsunto(s)
Quistes del Sistema Nervioso Central/diagnóstico , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Sensorineural/etiología , Trastornos Psicomotores/etiología , Quistes del Sistema Nervioso Central/complicaciones , Electroencefalografía , Pérdida Auditiva Bilateral/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Psychiatric comorbidity in patients with headache contributes to poorer prognosis, chronification of disease, poor response to treatment, increased cost of treatment, and decreased quality of life. The purpose of the present study was to evaluate the depressive symptoms in adolescents with chronic and episodic migraines and healthy adolescents. The study was performed between November 2010 and November 2011. All patients completed a detailed headache questionnaire comprising of demographical and clinical data and were instructed to fill out a headache diary over a 2-month period. The subjects ranged in age from 13 to 19 years. To evaluate depression symptoms, all of the subjects were asked to fill out the Beck Depression Inventory (BDI). A total of 137 participants were evaluated; 44 had episodic migraine (EM), 46 had chronic migraine (CM) and 47 were control subjects. Patients with a history of chronic migraine had significantly higher scores on the BDI than the other participants. Patients with chronic migraine had BDI scores that were 8.8 points higher than controls [95 % CI (ß) = 5.0, 12.6] and 5.8 points higher than patients with EM [95 % CI (ß) = 2.2, 9.4]. The main finding of this study was that chronic migraine is strongly associated with depression symptoms, regardless of demographic data. Comorbid depression may increase the total burden of migraine and diagnosis and treatment of depression in adolescents with migraine is likely to result in a better prognosis.
Asunto(s)
Depresión/complicaciones , Trastorno Depresivo/complicaciones , Trastornos Migrañosos/complicaciones , Adolescente , Depresión/psicología , Trastorno Depresivo/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Trastornos Migrañosos/psicología , Escalas de Valoración Psiquiátrica , Encuestas y Cuestionarios , Adulto JovenRESUMEN
A 10-year-old boy presented to our hospital with a 3-year history of fall attacks triggered by laughing, leading to a generalized loss of muscle tone without loss of consciousness (video). One year later, motor delayed skills started. Examination showed ataxia, moderate cognitive impairment, and vertical gaze palsy. EEG revealed diffuse slowing and disorganization of background rhythms. Molecular analysis disclosed heterozygosis p.P1007A and p.A1035V mutations, diagnostic of Niemann-Pick disease type C (NPC).
Asunto(s)
Cataplejía/diagnóstico , Cataplejía/etiología , Enfermedad de Niemann-Pick Tipo C/complicaciones , Enfermedad de Niemann-Pick Tipo C/diagnóstico , Cataplejía/genética , Niño , Humanos , Risa , Masculino , Enfermedad de Niemann-Pick Tipo C/genética , Grabación de Cinta de Video/métodosAsunto(s)
Cerebelo/patología , Inestabilidad Genómica , Lamina Tipo B/genética , Leucoencefalopatías/genética , Leucoencefalopatías/patología , Adulto , Cisplatino/efectos adversos , Daño del ADN/efectos de los fármacos , Femenino , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrógeno/efectos adversos , Lamina Tipo B/biosíntesis , Leucoencefalopatías/metabolismo , Mutación Missense , Cultivo Primario de Células , Temozolomida/efectos adversos , Secuenciación del ExomaRESUMEN
Herpes simplex encephalitis is a potentially fatal infection of central nervous system that typically involves frontal and temporal lobes. Occasionally, it presents an extratemporal involvement and in rarer cases, it is limited to the brainstem. We describe a case of an adolescent who presented with fever, sore throat, and vertigo. Clinical picture evolved to lethargy, tetraparesis, consciousness impairment, and respiratory failure. MRI showed lesions restricted to the brainstem. PCR of CSF was positive for herpes simplex type 1.
RESUMEN
Os autores relatam um caso de paciente portador de adenocarcinoma gástrico que foi submetido a uma gastrectomia total. Após três anos, apresentou recidiva logo abaixo da linha de sutura. Foi reoperado, e realizada ressecção com intenção curativa. Cinco anos após a segunda operação, o paciente encontrava-se assintomático e sem sinais de recorrência da doença. O adenocarcinoma é o tumor maligno mais comum do estômago e o tratamento consiste na ressecção cirúrgica. A recidiva local de adenocarcinoma gástrico indica que a ressecção cirúrgica não foi bem sucedida. A freqüência da recidiva local na literatura é variável, de 10 a 36%, e é influenciada pela localização do tumor, presença de margem de ressecção comprometida e extensão da margem de segurança. O diagnóstico da recidiva é feito pela história clínica e exames complementares. A abordagem cirúrgica apresenta, na maioria das vezes, resultados insatisfatórios. O intervalo livre de doença está diretamente relacionado com a ressecabilidade. O prognóstico depende do estadiamento do tumor, do tratamento cirúrgico e do intervalo livre de doença.
The autors report a case of a patient with gastric adenocarcinoma treated with total gastrectomy. Three years later, presented recurrence below the anastomosis line. Re-explorationand resection with curative purpose were done. Five years after the second surgical resection, the pacient has nosymptoms and no recurrence sign of disease. Adenocarcinoma is the most common malignant gastric tumor and itstreatment is surgical resection. Local recurrence of gastric adenocarcinoma denotes that surgical resection was notsuccessful. The rate in literature varies from 10 to 36% and is influenced by tumor location, resection margin involved by disease and tumor-free margin extension. Recurrence diagnosis is based on clinical history and complementary exams. The major surgical approach has unsatisfying results. The median disease-free interval is straightly related to resecability. Prognosis of gastric adenocarcinoma local recurrence depends on tumor staging, surgical treatment and disease-free interval.