RESUMO
Platelet function disorders (PFDs) are a common cause of mild bleeding tendency. However, they cannot be recognized by standard screening studies. The gold standard test for PFD is platelet aggregation, performed by light transmission aggregometry (LTA). A newer and less validated method is the closure time (CT), performed by the platelet function Analyzer 100 (PFA-100). Data regarding the validity of these tests in children are limited. The aim of this study was to evaluate the usefulness of LTA and PFA-100 for the diagnosis of pediatric patients with bleeding tendency. This retrospective study included patients one month-18 year old that had LTA tests performed at the coagulation laboratory of Rabin Medical Center between the years 2006-2015. Bleeding severity was assessed using a pediatric bleeding score. Patients were excluded from analysis if they had thrombocytopenia, thrombocytosis or coagulation factors deficiencies. One hundred and thirty-seven (137) patients were included in the analysis. The median age was 7.5 years (range one month-18 years). Most patients (93%) had a bleeding score of 2 or more. Abnormal LTA was found in 40% and prolonged CT in 23% of the patients. Abnormal LTA was significantly more common in patients with a bleeding score of 2 or more compared to patients with a lower bleeding scores (P = 0.04). No significant correlation was found between the bleeding severity and the number of agonists which induced abnormal responses (p = 0.52) or the CT (p = 0.35). Furthermore, no correlation was found between abnormal LTA and prolonged CT. To conclude, we were able to diagnose 40% of children who presented with bleeding tendency with platelet aggregation defects by LTA. Abnormal LTA was significantly more prevalent in patients with a bleeding score of 2 and above. In contrast, CT was not found to be sensitive as a screening tool for PFD. Therefore, our data extend the validity of the use of LTA for the evaluation of pediatric patients with bleeding tendency.
Assuntos
Plaquetas/patologia , Hemorragia/diagnóstico , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Adolescente , Ácido Araquidônico/farmacologia , Automação Laboratorial , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Criança , Pré-Escolar , Epinefrina/farmacologia , Feminino , Hemorragia/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Função Plaquetária , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated. RESULTS: All 27 Roma and eight non-Roma patients were homozygous for the common mutation c.317-2A > G. Five patients were compound heterozygotes for the common mutation and mutations c.470 T > A, c.628A > C, c.118_119insGT or c.251delC. Six Arab Muslims and two Turkish patients were homozygous for mutations c.238C > T, c.316 + 1G > T, c.336 T > A, c.578_579delCA, c.535C > T, c.359delC. Age of onset was neonatal in 41 patients, infantile in six cases and two years in one child. The most frequent symptoms at onset were poor feeding, hypotonia, lethargy, respiratory and heart failure, accompanied by lactic acidosis, 3-methylglutaconic aciduria and hyperammonaemia. Symptoms further included: developmental delay (98%), hypotonia (95%), faltering growth (94%), short stature (89%), non-progressive cardiomyopathy (89%), microcephaly (71%), facial dysmorphism (66%), hypospadias (50% of the males), persistent pulmonary hypertension of the newborn (22%) and Wolff-Parkinson-White syndrome (13%). One or more acute metabolic crises occurred in 24 surviving children, frequently followed by developmental regression. Hyperammonaemic episodes responded well to infusion with glucose and lipid emulsion, and ammonia scavengers or haemodiafiltration. Ten-year survival was 63%, importantly for prognostication, no child died after the age of five years. CONCLUSION: TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.
Assuntos
Hiperamonemia/genética , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas Mitocondriais/deficiência , Proteínas Mitocondriais/genética , Músculo Esquelético/patologia , Acidose Láctica/genética , Adolescente , Adulto , Cardiomiopatias/genética , Criança , Pré-Escolar , Gerenciamento Clínico , Europa (Continente) , Feminino , Heterozigoto , Homozigoto , Humanos , Lactente , Recém-Nascido , Israel , Estimativa de Kaplan-Meier , Masculino , Erros Inatos do Metabolismo/genética , Mutação , Estudos Retrospectivos , Turquia , Adulto JovemRESUMO
Neonatal diabetes mellitus is known to have over 20 different monogenic causes. A syndrome of permanent neonatal diabetes along with primary microcephaly with simplified gyral pattern associated with severe infantile epileptic encephalopathy was recently described in two independent reports in which disease-causing homozygous mutations were identified in the immediate early response-3 interacting protein-1 (IER3IP1) gene. We report here an affected male born to a non-consanguineous couple who was noted to have insulin-requiring permanent neonatal diabetes, microcephaly, and generalized seizures. He was also found to have cortical blindness, severe developmental delay and numerous dysmorphic features. He experienced a slow improvement but not abrogation of seizure frequency and severity on numerous anti-epileptic agents. His clinical course was further complicated by recurrent respiratory tract infections and he died at 8 years of age. Whole exome sequencing was performed on DNA from the proband and parents. He was found to be a compound heterozygote with two different mutations in IER3IP1: p.Val21Gly (V21G) and a novel frameshift mutation p.Phe27fsSer*25. IER3IP1 is a highly conserved protein with marked expression in the cerebral cortex and in beta cells. This is the first reported case of compound heterozygous mutations within IER3IP1 resulting in neonatal diabetes. The triad of microcephaly, generalized seizures, and permanent neonatal diabetes should prompt screening for mutations in IER3IP1. As mutations in genes such as NEUROD1 and PTF1A could cause a similar phenotype, next-generation sequencing approaches-such as exome sequencing reported here-may be an efficient means of uncovering a diagnosis in future cases.
Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus/genética , Epilepsia Generalizada/etiologia , Mutação da Fase de Leitura , Doenças do Recém-Nascido/genética , Proteínas de Membrana/genética , Microcefalia/etiologia , Mutação Puntual , Substituição de Aminoácidos , Cegueira Cortical/etiologia , Deficiências do Desenvolvimento/etiologia , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Epilepsia Generalizada/fisiopatologia , Epilepsia Generalizada/terapia , Evolução Fatal , Heterozigoto , Humanos , Recém-Nascido , Doenças do Recém-Nascido/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Microcefalia/terapia , Manifestações Neurológicas , Índice de Gravidade de DoençaRESUMO
The current study aimed to define evidence-based admission criteria of pediatric Henoch-Schonlein purpura (HSP). In addition, we aimed to better characterize epidemiological and clinical features of pediatric HSP in Israel. We performed a retrospective cohort study of all children with HSP admitted during a 15 years period to a single pediatric department. We strictly collected the clinical data of all HSP cases. Each case was categorized as either "necessary admission" or "unnecessary admission." We compared the two groups, using initially Chi square (χ(2)) and student "t" tests, and thereafter, we employed logistic stepwise regression analysis. One hundred and sixty-three children with HSP were included. A set of six clinical criteria of which the presence of minimum one predicts the need for hospitalization were identified including: orchitis, moderate or severe abdominal pain, arthritis involving more than two joints, proteinuria, clear evidence of gastrointestinal bleeding, and inability to ambulate. In conclusion, we suggest a predictive model for the admission of pediatric patients with acute HSP. The implementation of this model can significantly reduce unnecessary admissions.
Assuntos
Técnicas de Apoio para a Decisão , Vasculite por IgA/diagnóstico , Admissão do Paciente/normas , Adolescente , Fatores Etários , Anti-Inflamatórios não Esteroides/uso terapêutico , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Humanos , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/epidemiologia , Lactente , Israel/epidemiologia , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Procedimentos DesnecessáriosRESUMO
Alström syndrome (ALMS) is a rare autosomal recessive disorder caused by mutations in the ALMS1 gene. We report two brothers, 3 and 4 years of age and diagnosed with ALMS, who initially presented in infancy with severe dilated cardiomyopathy during febrile respiratory infection. The disease course in the two siblings was marked by significant intrafamilial variability. Although cardiomyopathy in the older sibling has mainly resolved thus allowing for the discontinuation of medical therapy, heart function in the younger sibling continues to deteriorate despite maximal drug support with furosemide, carvedilol, captopril, and aldospirone. Genetic analysis revealed homozygous mutations, c.8008C>T (R2670X), in ALMS1 resulting in premature protein truncation. This report further emphasizes the exceptional intrafamilial variability of ALMS, mainly during the natural course of cardiac disease.
Assuntos
Síndrome de Alstrom/diagnóstico , Cardiomiopatia Dilatada/diagnóstico , Códon sem Sentido , DNA/genética , Proteínas/genética , Irmãos , Síndrome de Alstrom/complicações , Síndrome de Alstrom/genética , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/genética , Proteínas de Ciclo Celular , Pré-Escolar , Análise Mutacional de DNA , Ecocardiografia , Homozigoto , Humanos , MasculinoRESUMO
BACKGROUND: The TMEM70 gene defect was recently identified as a novel cause of autosomal recessive ATP synthase deficiency. Most of the 28 patients with TMEM70 disorder reported to date display a distinctive phenotype characterised by neonatal onset of severe muscular hypotonia hypertrophic cardiomyopathy, facial dysmorphism, profound lactic acidosis, and 3-methylglutaconic aciduria. Almost all share a common Roma descent and are homozygous for a single founder splice site mutation. METHODS: Six new patients from four separate families, with clinical and biochemical diagnosis of ATP synthase deficiency, were studied. TMEM70 sequence analysis of the three exons and their flanking splice junction consensus sequences was performed in all patients. In addition their clinical phenotype and disease course was strictly studied. RESULTS: Four novel deleterious homozygous TMEM70 mutations were identified. The previously described clinical spectrum was expanded to include infantile onset cataract, early onset gastrointestinal dysfunction and congenital hypertonia with multiple contractures resembling arthrogryposis. The first characterisation of fetal presentation of the syndrome is also provided, featuring significant intrauterine growth retardation, severe oligohydramnios, fetal hypotonia, and myocardial wall thickening. CONCLUSIONS: The current report corroborates the previously described unique phenotype of TMEM70 deficiency. The study identifies TMEM70 gene defect as a pan-ethnic disorder and further redefines it as the most common cause of nuclear-origin ATP synthase deficiency.
Assuntos
Núcleo Celular/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Mutação , ATPases Translocadoras de Prótons/deficiência , Acidose Láctica/genética , Cardiomiopatia Hipertrófica/genética , Núcleo Celular/metabolismo , Pré-Escolar , Consanguinidade , Etnicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Membrana/metabolismo , Erros Inatos do Metabolismo/genética , Proteínas Mitocondriais/metabolismo , Síndrome , Adulto JovemRESUMO
Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy.
Assuntos
Corpo Estriado/patologia , Lateralidade Funcional/genética , Proteínas de Membrana Transportadoras/genética , Mutação de Sentido Incorreto/genética , Polineuropatias/genética , Adolescente , Adulto , Doenças dos Gânglios da Base/diagnóstico , Doenças dos Gânglios da Base/genética , Doenças dos Gânglios da Base/patologia , Criança , DNA Mitocondrial/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Microcefalia/genética , Proteínas de Transporte da Membrana Mitocondrial , Dados de Sequência Molecular , Necrose/genética , Necrose/patologia , Linhagem , FenótipoRESUMO
BACKGROUND: Human parvovirus B19 is a global and common infectious pathogen in humans, particularly in children. OBJECTIVES: To assess the immunoglobulin G3 seroprevalence of B19 in children in Israel. METHODS: Overall, 128 previously healthy children (1.5-17 years old) hospitalized for various diseases other than acute human parvovirus B19 infection were assessed for IgG to the virus by enzyme-linked immunosorbent assay. RESULTS: The IgG seroprevalence increased from 22% in children aged 1.5-9 years to 52% in older children (P = 0.001). CONCLUSIONS: Our data suggest that most acute parvovirus B19 infections in Israel occur in the early school years, and that by 18 years of age 50% of Israeli children have been infected by the virus.
Assuntos
Imunoglobulina G/sangue , Infecções por Parvoviridae/epidemiologia , Parvovirus B19 Humano/isolamento & purificação , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Israel/epidemiologia , Masculino , Infecções por Parvoviridae/sangue , Estudos Prospectivos , Estudos SoroepidemiológicosRESUMO
We report on three individuals of Muslim Arab origin from a village located in Northern Israel affected by an apparent autosomal recessive syndrome characterized by distinctive facial phenotype of which the most prominent feature is ocular hypertelorism. The other clinical features of the syndrome include variable degree of mental retardation, genital abnormalities dominated by short penis, and skeletal abnormalities including chest deformity (combination of upper pectus carinatum with lower pectus excavatum), and short palms with broad short fingers. Affected individuals displayed distinctive facial features including upslanting palpebral fissures, thick eyebrows, long philtrum, wide mouth with thin upper lip and upturned corners of the mouth, widow's peak, broad nasal bridge, and simple ears with fleshy overfolded helices. This phenotype does not fully meet typical diagnostic features of any known condition.
Assuntos
Anormalidades Múltiplas/genética , Fácies , Genes Recessivos/genética , Genitália/anormalidades , Deformidades Congênitas da Mão/complicações , Hipertelorismo/complicações , Deficiência Intelectual/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Deformidades Congênitas da Mão/genética , Humanos , Hipertelorismo/genética , Deficiência Intelectual/genética , Masculino , Linhagem , Síndrome , Adulto JovemRESUMO
Pylephlebitis, a septic thrombophlebitis of the portal vein, is a life-threatening complication of intraabdominal infections, commonly associated with acute appendicitis in children, and diverticulitis in adults. A 13-year-old boy was admitted for high fever and jaundice. On the fifth day of hospitalization, ultrasound Doppler flow and Computer Tomography scan studies showed thrombosis of the portal vein and acute appendicitis. The patient was treated with antibiotics, anticoagulation and laparotomy with appendectomy. No thrombophilic risk factors were diagnosed. Our aim is to improve physicians' awareness of this complication and emphasize the importance of early diagnosis and appropriate therapy in children in order to reduce serious complications and long-term sequels.
Assuntos
Apendicite/complicações , Sepse/complicações , Sepse/etiologia , Tromboflebite/complicações , Tromboflebite/etiologia , Adolescente , Anticoagulantes/uso terapêutico , Apendicite/diagnóstico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Protrombina/metabolismo , Tromboflebite/tratamento farmacológico , Ultrassonografia DopplerRESUMO
A child suffered from herpes simplex virus encephalitis at the age of 6 months; a late relapse occurred 8.5 years after the initial episode, the longest latency period reported. Radiologic and autopsy findings suggest local reactivation of latent herpes simplex virus as the cause of relapse. All cases of late relapse of herpes simplex virus encephalitis in the last 15 years are reviewed, with emphasis on clinical characteristics and possible mechanisms.
Assuntos
Encefalite por Herpes Simples , Herpes Simples , Herpesvirus Humano 1/patogenicidade , Ativação Viral , Latência Viral , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Criança , Evolução Fatal , Herpesvirus Humano 1/fisiologia , Humanos , Lactente , Masculino , RecidivaRESUMO
AIMS: To determine if familial Mediterranean fever (FMF) genetic testing should be advised in children with initial presentation of monoarthritis and to identify clinical parameters associated with FMF-induced arthritis that warrant genetic investigation. METHODS: A prospective study of 71 otherwise healthy children admitted to our pediatric department between 2010-2013 with a first episode of idiopathic monoarthritis. Demographic, clinical and laboratory data were documented and genetic assay of the five common mutations in our population of the MEFV gene that cause FMF syndrome were analyzed in the entire study population. Statistical analysis compared two groups according to FMF status (FMF arthritis and idiopathic arthritis). RESULTS: Among the cohort seven (10%) children harbored two pathogenic mutations in the MEFV gene, thus confirming diagnosis of FMF. This FMF-induced arthritis group had a statistically significant female predominance compared with the idiopathic arthritis group (six [86%] vs. 19 [30%], respectively) (P = 0.006, odds ration [OR] = 14.2). In addition, associated abdominal pain during the attack (two [28%] vs. two [3%], respectively) (P = 0.04, OR = 12.4) and a family history of FMF (two [29%] vs. five [8%], respectively) (P = 0.1, OR 4.7,) were more common in the FMF-induced arthritis group. CONCLUSIONS: In Mediterranean populations where FMF is relatively common we recommend for every child with a first episode of arthritis, without an identifying cause to strongly consider MEFV genetic testing of the common mutations in the relevant population.
Assuntos
Artrite/diagnóstico , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/diagnóstico , Testes Genéticos/métodos , Mutação , Pirina/genética , Artrite/epidemiologia , Artrite/genética , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Lactente , Israel/epidemiologia , Masculino , Razão de Chances , Fenótipo , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: The extent and clinical manifestations of acute human parvovirus B19 (B19) infection were assessed in previously healthy hospitalized children admitted with clinical syndromes potentially associated the virus. PATIENTS AND METHODS: The study was prospective and was conducted between October 2002 and August 2004 in the pediatric departments of 3 hospitals in Israel. The survey included previously healthy children who were hospitalized with 1 or more of the following acute diseases: acute nonallergic exanthema, fever for >1 week, aplastic anemia or pancytopenia, acute nonbacterial arthropathy, immune thrombocytopenic purpura (ITP), Henoch-Schönlein purpura (HSP) and aseptic meningitis. A control group of children with a proven, non-B19 infection was also studied. Serum samples obtained from each child on admission were tested for B19 DNA by real-time PCR and B19 IgM by ELISA. Acute B19 infection was defined by the following criteria: positive serum B19-DNA and/or B19 IgM, negative serum B19 IgG, and no other proven infection. RESULTS: Overall, 167 children were included in the study. The mean age was 5.5 +/- 4.6 years (range, 0.5-17), males and females equally divided. Acute B19 infection was demonstrated in 12.6% (n = 21) of the children. Both tests were performed in 19 children and were positive in 10 (53%). In 7 and 2 children, only B19-DNA or B19 IgM, respectively, was positive. Acute B19 infection was documented in 27% (10/39) of children who presented with a variety of acute exanthema diseases; 9% (5/57) of children with acute arthropathy (all 5 had transient synovitis); 10% (2/21) of children with fever >1 week, both presented as mononucleosis syndrome; and in 44% (4/9) of children with transient pancytopenia or aplastic anemia. No acute B19 infection was demonstrated in 15 children with ITP, 9 with HSP, and 6 with aseptic meningitis and among 70 children in the control group. By logistic regression analysis, manifestations significantly associated with acute B19 infection were exanthema (OR 2.9; 95% CI = 1.1-7.5), anemia (OR 6.35; 95% CI = 2.2-18.2) and leucopenia (OR 4.14; 95% CI =1.2-14.2). CONCLUSIONS: Acute B19 infection was documented among 12.6% of children hospitalized with clinical syndrome potentially associated with the virus. Clinical and laboratory features associated with acute B19 infection were exanthema, anemia and leucopenia. Determination of both serum B19-DNA and serum B19 IgM should be performed for the accurate diagnosis of acute B19 infection.
Assuntos
Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Adolescente , Anemia Aplástica/virologia , Anticorpos Antivirais/sangue , Artrite/virologia , Criança , Pré-Escolar , DNA Viral/sangue , Ensaio de Imunoadsorção Enzimática , Exantema/virologia , Feminino , Febre , Humanos , Vasculite por IgA/virologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Modelos Logísticos , Masculino , Meningite Asséptica/virologia , Pancitopenia/virologia , Infecções por Parvoviridae/fisiopatologia , Parvovirus B19 Humano/imunologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Púrpura Trombocitopênica/virologia , Estudos SoroepidemiológicosRESUMO
We report a 22 year-old male with glycogen storage disease type 1 (GSD-1) who developed diabetes mellitus secondary to pancreatic islet beta-cell insufficiency. Diabetes mellitus should be considered among the late complications of GSD-1. The pathogenesis of the conversion, from a disease characterized by hypoglycemia to a disease dominated by hyperglycemia, is discussed.
Assuntos
Diabetes Mellitus/etiologia , Doença de Depósito de Glicogênio Tipo I/complicações , Adulto , Diabetes Mellitus/patologia , Doença de Depósito de Glicogênio Tipo I/patologia , Humanos , Hiperglicemia/etiologia , Ilhotas Pancreáticas/diagnóstico por imagem , Ilhotas Pancreáticas/patologia , Masculino , Pâncreas/diagnóstico por imagem , Testes de Função Pancreática , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care. OBJECTIVES: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment on hospitalization for acute asthma during this period. METHODS: All records of pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions RESULTS: There were 1584 admissions, 1208 were first-time admissions and 376 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease in re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates. CONCLUSIONS: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease its severity, morbidity, and resultant hospital admissions.
Assuntos
Asma/epidemiologia , Hospitalização/estatística & dados numéricos , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Hospitalização/tendências , Humanos , Lactente , Israel/epidemiologia , Tempo de Internação , Masculino , Readmissão do Paciente/estatística & dados numéricosRESUMO
We describe two cases of neonatal suppurative parotitis caused by Staphylococcus aureus. Only 32 cases of neonatal suppurative parotitis (72% male) have been described in the English literature in the last 35 years. Thirty-eight percent were premature babies, only 41% were febrile and the causative agent in most cases was S. aureus. Recovery was achieved in 78% of the patients with antibiotic therapy without drainage.
Assuntos
Parotidite/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Doença Aguda , Antibacterianos , Quimioterapia Combinada/administração & dosagem , Seguimentos , Humanos , Recém-Nascido , Masculino , Parotidite/tratamento farmacológico , Parotidite/microbiologia , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Isolated metabolic myopathies encompass a heterogeneous group of disorders, with mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy production manifesting either by recurrent episodes of myoglobinuria or progressive muscle weakness. In this study, we investigated the genetic cause of a patient from a consanguineous family who presented with adolescent onset autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the five respiratory chain complexes in our patients' skeletal muscle showed severely impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and mitochondrial aconitase. We employed exome sequencing combined with homozygosity mapping to identify a homozygous mutation, c.1A>T, in the FDX1L gene, which encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the ATG initiation translation site resulting in severe reduction of Fdx2 content in the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of the Fe-S cluster biogenesis machinery, the first being IscU that is associated with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L in cases of mitochondrial myopathy especially when associated with reduced activity of the respiratory chain complexes I, II and III.
Assuntos
Ferredoxinas/genética , Miopatias Mitocondriais/genética , Proteínas Mitocondriais/genética , Mutação Puntual , Adolescente , Análise Mutacional de DNA , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/metabolismo , Exoma , Feminino , Ferredoxinas/metabolismo , Humanos , Miopatias Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismoRESUMO
Neuronal ceroid lipofuscinosis (NCL) refers to a growing heterogeneous group of neurodegenerative disorders characterized by lysosomal accumulation of abnormal autofluorescent material. NCLs are traditionally classified clinically according to their age of onset. Variable late infantile NCL (vLINCL) is the most genetically heterogeneous subtype as it has been shown to be caused by mutations in at least six genes. We report on 5 patients of a consanguineous family who presented in early childhood with intractable seizures, severe cognitive and motor decline, behavioral impairment and progressive retinal degeneration. Disease course was severe; all patients were in a vegetative state by the second decade of life, and eventually die prematurely (except in one case). Ultrastructural studies of brain and rectal mucosa disclosed accumulation of storage material in various patterns including fingerprint, curvilinear, and granular osmiophilic deposits consistent with the diagnosis of NCL. Brain pathologic features from a living patient are first reported here and shed light on disease progression and pathogenesis. Using a combination of whole genome autozygosity mapping and candidate gene direct sequencing, we identified a mutation in MFSD8, c.472G>A (p.Gly158Ser), which was found to segregate with the disease phenotype in the family. This study underscores the importance of a combined clinic-molecular workup in NCLs and other neurodegenerative conditions.
Assuntos
Proteínas de Membrana Transportadoras/genética , Lipofuscinoses Ceroides Neuronais/genética , Adolescente , Consanguinidade , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Humanos , Masculino , Mutação de Sentido Incorreto , Lipofuscinoses Ceroides Neuronais/patologia , Linhagem , Adulto JovemRESUMO
Recurrent reactivation of latent Varicella-Zoster virus may cause various neurological complications including encephalitis, myelitis, stroke episodes, and meningitis. It occurs mainly in elderly or immunocompromised patients and is very rare in children. We report a 14-year girl who presented with meningoencephalitis due to reactivation of Varicella-Zoster virus 10 years after she had chickenpox and 4 years after she had zoster. Characteristic skin lesions of varicella were absent. Varicella-Zoster virus DNA was detected in cerebrospinal fluid and magnetic resonance imaging (MRI) findings were consistent with small vessel cerebral vasculitis. Treatment with acyclovir and high dose methylprednisolone resulted in near-complete neurological recovery. Although rare, Varicella-Zoster virus may reactivate to cause significant central nervous system disease even in immunocompetent children. Diagnosis depends on a high degree of suspicion because the typical rash may not associate the disease. Characteristic lesions on MRI and the presence of Varicella-Zoster virus DNA in cerebrospinal fluid are key findings for the correct diagnosis.