RESUMO
Congenital disorders of glycosylation type I (CDG-I) form a growing group of recessive neurometabolic diseases. Identification of disease genes is compromised by the enormous heterogeneity in clinical symptoms and the large number of potential genes involved. Until now, gene identification included the sequential application of biochemical methods in blood samples and fibroblasts. In genetically unsolved cases, homozygosity mapping has been applied in consanguineous families. Altogether, this time-consuming diagnostic strategy led to the identification of defects in 17 different CDG-I genes. Here, we applied whole-exome sequencing (WES) in combination with the knowledge of the protein N-glycosylation pathway for gene identification in our remaining group of six unsolved CDG-I patients from unrelated non-consanguineous families. Exome variants were prioritized based on a list of 76 potential CDG-I candidate genes, leading to the rapid identification of one known and two novel CDG-I gene defects. These included the first X-linked CDG-I due to a de novo mutation in ALG13, and compound heterozygous mutations in DPAGT1, together the first two steps in dolichol-PP-glycan assembly, and mutations in PGM1 in two cases, involved in nucleotide sugar biosynthesis. The pathogenicity of the mutations was confirmed by showing the deficient activity of the corresponding enzymes in patient fibroblasts. Combined with these results, the gene defect has been identified in 98% of our CDG-I patients. Our results implicate the potential of WES to unravel disease genes in the CDG-I in newly diagnosed singleton families.
Assuntos
Defeitos Congênitos da Glicosilação/genética , Exoma , Genoma Humano , Análise de Sequência de DNA , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Defeitos Congênitos da Glicosilação/metabolismo , Feminino , Glicosilação , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Proteínas/genética , Proteínas/metabolismo , Adulto JovemRESUMO
The primary purpose of this work was to assess long-term in vitro reproducibility of metabolite levels measured using 1H MRS (proton magnetic resonance spectroscopy). The secondary purpose was to use the in vitro results for interpretation of 1H MRS in vivo spectra acquired from patients diagnosed with Canavan disease. 1H MRS measurements were performed in the period from April 2006 to September 2010. 118 short and 116 long echo spectra were acquired from a stable phantom during this period. Change-point analysis of the in vitro N-acetylaspartate levels was exploited in the computation of fT factor (ratio of the actual to the reference N-acetylaspartate level normalized by the reciprocity principle). This coefficient was utilized in the interpretation of in vivo spectra analyzed using absolute reference technique. The monitored time period was divided into six time intervals based on short echo in vitro data (seven time intervals based on long echo in vitro data) characterized by fT coefficient ranging from 0.97 to 1.09 (based on short echo data) and from 1.0 to 1.11 (based on long echo data). Application of this coefficient to interpretation of in vivo spectra confirmed increased N-acetylaspartate level in Canavan disease. Long-term monitoring of an MRS system reproducibility, allowing for absolute referencing of metabolite levels, facilitates interpretation of metabolic changes in white matter disorders.
Assuntos
Ácido Aspártico/análogos & derivados , Encéfalo/metabolismo , Doença de Canavan/diagnóstico , Doença de Canavan/metabolismo , Diagnóstico por Computador/métodos , Espectroscopia de Prótons por Ressonância Magnética/instrumentação , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Algoritmos , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Técnicas In Vitro , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Pesquisa Translacional Biomédica , Adulto JovemRESUMO
Mucopolysaccharidosis 1 (MPS 1) is a group of rare lysosomal genetic disorders resulting from the accumulation of undegraded glycosaminoglycans (GAGs) leading to multiorgan damage. Neurological symptoms vary from mild to severe. Neuroimaging-mainly magnetic resonance (MRI)-plays a crucial role in disease diagnosis and monitoring. Early diagnosis is of the utmost importance due to the necessity of an early therapy implementation. New imaging tools like MR spectroscopy (MRS), semiquantitative MRI analysis and applying scoring systems help substantially in MPS 1 surveillance. The presented analysis of neuroimaging manifestations is based on 5 children with MPS 1 and a literature review. The vigilance of the radiologist based on knowledge of neuroradiological patterns is highlighted.
RESUMO
The cerebellum plays a role not only in motor control but also in motor learning and cognition. Joubert syndrome is a rare heterogeneous inherited genetic disorder characterized by ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances or abnormal eye movement. The estimated frequency of Joubert syndrome in the United States is around 1 : 100 000. The term Joubert syndrome and related disorders (JSRD) has been recently coined to describe all disorders presenting with molar tooth sign on brain neuroimaging. Joubert syndrome is believed to be a representative of a new group of disorders named ciliopathies. The identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) has led to substantial progress in the understanding of the genetic basis of Joubert syndrome. The authors focus on clinical presentation of JSRD, differential diagnosis and molecular background.
Assuntos
Doenças Cerebelares/diagnóstico , Doenças Cerebelares/genética , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/genética , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Anormalidades Múltiplas , Cerebelo/anormalidades , Humanos , Retina/anormalidadesRESUMO
INTRODUCTION: The aim of this study was to evaluate the prevalence of selected risk factors of weight deficiency in children with chronic metabolic diseases. MATERIAL AND METHODS: The study group involved 160 children, from 2 months to 15 years (mean age 3.14 years), with diseases of the nervous system and body weight deficiency. According to the type of neurological disease the following groups of patients were separated: static encephalopathies, progressive encephalopathies, disorders of mental development of undetermined etiology, genetically determined diseases. As the exponent of malnutrition, z-score of weight-for-age standards was used. An inclusion criterion for the study group was z-score of weight-for-age < - 2SD. The analysed risk factors of body weight deficiency were: mode of feeding children, neurological disorders, oral motor dysfunction, diseases of other organs, gastrointestinal motility disorders (oral cavity, esophagus, intestines) and type of nutritional therapy. RESULTS: The most advanced malnutrition was in children with progressive encephalopathies and genetically determined diseases. Seizures and muscular hypotonia were most common neurological disorders. Oral motor dysfunctions were observed in 40% of patients. CONCLUSIONS: Malnutrition in children with neurological disorders is associated mainly with neurological deficits. In this group of children monitoring of somatic development and early nutritional intervention are necessary.
Assuntos
Transtornos da Nutrição Infantil/prevenção & controle , Métodos de Alimentação/classificação , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Transtornos da Nutrição do Lactente/prevenção & controle , Doenças do Sistema Nervoso/epidemiologia , Terapia Nutricional/métodos , Adolescente , Causalidade , Criança , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/etiologia , Pré-Escolar , Comorbidade , Constipação Intestinal/epidemiologia , Constipação Intestinal/prevenção & controle , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/prevenção & controle , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/prevenção & controle , Humanos , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Masculino , Estado Nutricional , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Fatores de Risco , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controleRESUMO
BACKGROUND: ALG13-CDG belongs to the congenital disorders of glycosylation (CDG), which is an expanding group of multisystemic metabolic disorders caused by the N-linked, O-linked oligosaccharides, shared substrates, glycophosphatidylinositol (GPI) anchors, and dolichols pathways with high genetic heterogeneity. Thus, as far as clinical presentation, laboratory findings, and treatment are concerned, many questions are to be answered. Three individuals presented here may serve as a good example of clinical heterogeneity. This manuscript describes the first metabolomic analysis using NMR in three patients with epileptic encephalopathy due to the recurrent c.320A>G variant in ALG13, characterized to date only in about 60 individuals (mostly female). This is an important preliminary step in the understanding of the pathogenesis of the disease associated with this variant in the rare genetic condition. The disease is assumed to be a disorder of N-glycosylation given that this is the only known function of the ALG13 protein. Despite this, protein electrophoresis, which is abnormal in most conditions due to abnormalities in N-glycosylation, has been normal or only mildly abnormal in the ALG13 patients. METHODS: Nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate and univariate modelling were used to analyze the metabolic profile of the blood serum samples acquired from the studied patients. RESULTS: Three metabolites were identified as potential biomarkers: betaine, N-acetyl-glycoprotein, and carnitine. CONCLUSIONS: Since presented data are the first to be collected so far, they need be verified in further studies. Our intention was to turn attention toward possible CDG-ALG13 laboratory markers that would have clinical significance.
RESUMO
Congenital microcephaly causes smaller than average head circumference relative to age, sex and ethnicity and is most usually associated with a variety of neurodevelopmental disorders. The underlying etiology is highly heterogeneous and can be either environmental or genetic. Disruption of any one of multiple biological processes, such as those underlying neurogenesis, cell cycle and division, DNA repair or transcription regulation, can result in microcephaly. This etiological heterogeneity manifests in a clinical variability and presents a major diagnostic and therapeutic challenge, leaving an unacceptably large proportion of over half of microcephaly patients without molecular diagnosis. To elucidate the clinical and genetic landscapes of congenital microcephaly, we sequenced the exomes of 191 clinically diagnosed patients with microcephaly as one of the features. We established a molecular basis for microcephaly in 71 patients (37%), and detected novel variants in five high confidence candidate genes previously unassociated with this condition. We report a large number of patients with mutations in tubulin-related genes in our cohort as well as higher incidence of pathogenic mutations in MCPH genes. Our study expands the phenotypic and genetic landscape of microcephaly, facilitating differential clinical diagnoses for disorders associated with most commonly disrupted genes in our cohort.
Assuntos
Sequenciamento do Exoma/métodos , Redes Reguladoras de Genes , Microcefalia/genética , Mutação , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/diagnóstico por imagem , Linhagem , Análise de Sequência de DNARESUMO
BACKGROUND: The aim of the study was to assess diurnal melatonin secretion in children with refractory epilepsy (N=74) as compared to children without epileptic seizures (N=37) and to compare melatonin secretion in children with focal and generalized refractory epilepsy. MATERIAL/METHODS: In the study group 4 subgroups were defined: children with focal symptomatic epilepsy, focal cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA method. RESULTS: Analysis of diurnal melatonin secretion indicated a lower level of the hormone in patients with refractory epilepsy. The daily rhythm of melatonin secretion in the study group was maintained, with a peak shift of melatonin secretion especially visible in the subgroup with generalized symptomatic refractory epilepsy in the age group between 6 months and 3 years of age. CONCLUSIONS: The hypothesis may be formed that a lowered level of melatonin in the study group in relation to the comparison group is the consequence of the natural course of epilepsy or is influenced by antiepileptic drugs.
Assuntos
Epilepsia/metabolismo , Melatonina/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Ritmo Circadiano/fisiologia , Epilepsia/fisiopatologia , Epilepsia Generalizada/metabolismo , Epilepsia Generalizada/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Sono/fisiologiaRESUMO
CONCLUSION: VLCFA levels correlate with the severity of the clinical course of ZS, DBP and mild ZSD. The best predictive value for estimating the projected disease severity and survival time is a concentration of C26:0.
Assuntos
Biomarcadores/sangue , Ácidos Graxos/sangue , Transtornos Peroxissômicos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transtornos Peroxissômicos/diagnóstico , Transtornos Peroxissômicos/fisiopatologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto Jovem , Síndrome de Zellweger/diagnóstico , Síndrome de Zellweger/fisiopatologiaRESUMO
Sudden infant death syndrome (SIDS) remains still unsolved medical entity. At present about 80 theories and hypotheses concerning SIDS exist. The authors describe current opinions concerning SIDS pathogenesis and etiology.
Assuntos
Morte Súbita do Lactente/etiologia , Doenças Cardiovasculares/complicações , Humanos , Lactente , Recém-Nascido , Infecções/complicações , Doenças do Sistema Nervoso/complicações , Fatores de RiscoRESUMO
The maternal phenylketonuria (MPKU) syndrome is an example of biochemical teratogenesis caused by high phenylalanine concentrations in serum of a pregnant woman (over 360 micromol/L). Active transport through the placenta increases 1.5-fold the phenylalanine level in the child's blood as compared to concentrations recorded in the mother. Increased phenylalanine concentrations may lead to disorders in proliferation of neural cells, neuronal migrations and affect the process of synaptogenesis and myelination. The authors present two children with maternal phenylketonuria with a characteristic clinical picture. Particular attention was drawn to the fact of diagnosed phenylketonuria in mothers following a suspicion and diagnosis of maternal phenylketonuria in children, as well as the occurrence of refractory epilepsy in one of the patients. The mothers' average phenylalanine concentration exceeded the value of 1300 micromol/L, while in children it ranged between 117-160 micromol/L.
Assuntos
Epilepsia/diagnóstico , Fenilalanina/sangue , Fenilcetonúrias/sangue , Fenilcetonúrias/diagnóstico , Efeitos Tardios da Exposição Pré-Natal , Criança , Epilepsia/complicações , Feminino , Humanos , Lactente , Masculino , Fenilcetonúria Materna/sangue , Fenilcetonúrias/complicações , GravidezRESUMO
Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35-40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. 1H-NMR serum spectra were acquired on 400 MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.
Assuntos
Epilepsia Resistente a Medicamentos/metabolismo , Espectroscopia de Ressonância Magnética , Metabolômica , Criança , Pré-Escolar , Análise Discriminante , Epilepsia Resistente a Medicamentos/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Análise dos Mínimos Quadrados , Masculino , Redes e Vias Metabólicas , Metaboloma , Análise de Componente PrincipalRESUMO
Back pain and pain of the surrounding structures leads to significant diagnostic and therapeutic difficulties which result from a complex pathomechanism. They are the symptom of a large number of pathologic processes that may to a varying extent contribute to pain related manifestation of symptoms. In 80-90% of cases the cause of the back pain remains unknown, only in 10-20% adult patients it is feasible to establish the etiological factor during one year observation. Contrary to the situation in adults, in over 50% of children it is possible to identify the cause of the reported ailments. The authors present etiological factors and clinical symptoms in 44 patients, hospitalized because of back pain in Child Neurology Department of Medical University of Silesia in Katowice in the period between 2004 and 2007.
Assuntos
Dor Lombar/diagnóstico , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Adolescente , Desenvolvimento do Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Medição da Dor/métodos , Polônia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Malformations of cortical development (MCDs) manifest with structural brain anomalies that lead to neurologic sequelae, including epilepsy, cerebral palsy, developmental delay, and intellectual disability. To investigate the underlying genetic architecture of patients with disorders of cerebral cortical development, a cohort of 54 patients demonstrating neuroradiologic signs of MCDs was investigated. Individual genomes were interrogated for single-nucleotide variants (SNV) and copy number variants (CNV) with whole-exome sequencing and chromosomal microarray studies. Variation affecting known MCDs-associated genes was found in 16/54 cases, including 11 patients with SNV, 2 patients with CNV, and 3 patients with both CNV and SNV, at distinct loci. Diagnostic pathogenic SNV and potentially damaging variants of unknown significance (VUS) were identified in two groups of seven individuals each. We demonstrated that de novo variants are important among patients with MCDs as they were identified in 10/16 individuals with a molecular diagnosis. Three patients showed changes in known MCDs genes and a clinical phenotype beyond the usual characteristics observed, i.e., phenotypic expansion, for a particular known disease gene clinical entity. We also discovered 2 likely candidate genes, CDH4, and ASTN1, with human and animal studies supporting their roles in brain development, and 5 potential candidate genes. Our findings emphasize genetic heterogeneity of MCDs disorders and postulate potential novel candidate genes involved in cerebral cortical development.
Assuntos
Variações do Número de Cópias de DNA , Exoma , Malformações do Desenvolvimento Cortical/genética , Polimorfismo de Nucleotídeo Único , Caderinas/genética , Feminino , Heterogeneidade Genética , Humanos , Masculino , Malformações do Desenvolvimento Cortical/patologia , Proteínas do Tecido Nervoso/genética , Receptores de Superfície Celular/genéticaRESUMO
OBJECTIVES: Angelman syndrome (AS) is characterized by severe mental retardation, epilepsy, absent speech, dysmorphic facial features, and a characteristic behavioral phenotype. It is caused by deficiency of gene expression from maternally derived chromosome 15q11-q13. STUDY DESIGN: The authors present the clinical picture of 9 children (median age, 4.9 years; range, 1 to 10 years) with confirmed Angelman syndrome. The patients complied with the international consensus criteria for AS and were consecutively investigated for psychomotor development, epilepsy, and electroencephalogram (EEG) profiles. RESULTS: The median age at diagnosis was 3.9 years. The motor milestones were delayed. Median developmental quotient level was 26. All patients but 1 experienced predominantly polymorphic seizures. In 4 cases, the epilepsy was refractory to treatment. The EEG of all patients displayed an abnormal sleep pattern and generalized abnormalities, with a maximum over the posterior areas. CONCLUSIONS: Milder or less typical phenotypes of AS may remain undiagnosed, leading to an overall underdiagnosis of the disease. The EEG shows no clear relation to genotype, clinical picture, or to the presence and severity of epilepsy. AS should be considered in the differential diagnosis of children with severe cryptogenic epilepsy and a characteristic configuration of clinical features.
Assuntos
Síndrome de Angelman/fisiopatologia , Síndrome de Angelman/genética , Síndrome de Angelman/psicologia , Anticonvulsivantes/uso terapêutico , Comportamento , Criança , Pré-Escolar , Resistência a Medicamentos , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Genótipo , Humanos , Lactente , Deficiência Intelectual/etiologia , Deficiência Intelectual/psicologia , Imageamento por Ressonância Magnética , Masculino , Transtornos dos Movimentos/fisiopatologia , Fenótipo , Convulsões/fisiopatologia , Distúrbios da Fala/fisiopatologiaRESUMO
Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive neurodegenerative disorder with autosomal recessive inheritance. The major symptoms of PKAN include the onset before the age of 20 years, progressive pyramidal and extrapyramidal signs, retinitis pigmentosa, optic atrophy, dementia, and iron depositions in the globus pallidus. The authors present 3 patients with proven molecular diagnosis of PKAN, in whom 2 novel mutations of PANK2 gene have been identified.
Assuntos
Mutação , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Adolescente , Arginina/genética , Criança , Glicina/genética , Humanos , MasculinoRESUMO
Peroxisomal diseases are a heterogeneous group of genetic metabolic disorders which are caused by incorrect biogenesis of peroxisomes or a defect in activity of particular enzymes located in those organelles.D-bifunctional protein (D-BP) deficiency belongs to the second group of peroxisomal diseases characterised by dysfunction of a single peroxisomal enzyme. Bifunctional protein is a catalyst in the second and third stage of the beta-oxidation of fatty acids. Gene locus of bifunctional protein deficiency comprises chromosomes 5q2 and 3p23-p22. The authors present two siblings with progressing family encephalopathy. In the younger brother the diagnosis of a bifunctional protein deficiency was made. The girl died before a diagnosis was made;however, due to the presence of a very similar clinical condition a suspicion arises that the girl had a peroxisomal disease. In the siblings were ascertained characteristic dysmorphic features, delayed psychomotor development, polymorphic epileptic seizures and generalized muscular hypotonia with areflexia. The neuropathological findings were consistent in general with MRI findings showing features of hypomyelination. Also neuron heterotopias that were found in autopsy are a form of pathology typical for D-BP.
Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Oxirredutases/deficiência , Transtornos Peroxissômicos/patologia , Transtornos Peroxissômicos/fisiopatologia , Encéfalo/metabolismo , Feminino , Humanos , Lactente , Masculino , Transtornos Peroxissômicos/metabolismoRESUMO
Angelman Syndrome (AS, MIM 105830), classified among neurogenetic disorders, occurs with estimated frequency of 1:10 000 to 1:40 000. The characteristics features apart from neurodevelopmental impairment and seizures include peculiar face traits, absent speech, outburst of laughter, ataxia, stereotyped jerky (puppet-like) movements. The authors report three children with Angelman syndrome who were also diagnosed with hypothyroidism.
Assuntos
Síndrome de Angelman/complicações , Cromossomos Humanos Par 15/genética , Hipotireoidismo/complicações , Adolescente , Síndrome de Angelman/genética , Pré-Escolar , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/genética , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Deleção de Sequência , Tiroxina/uso terapêuticoRESUMO
Zellweger syndrome (ZS) is a consequence of a peroxisome biogenesis disorder (PBD) caused by the presence of a pathogenic mutation in one of the 13 genes from the PEX family. ZS is a severe multisystem condition characterized by neonatal appearance of symptoms and a shorter life. Here, we report a case of ZS with a mild phenotype, due to a novel PEX6 gene mutation. The patient presented subtle craniofacial dysmorphic features and slightly slower psychomotor development. At the age of 2 years, he was diagnosed with adrenal insufficiency, hypoacusis, and general deterioration. Magnetic resonance imaging showed a symmetrical hyperintense signal in the frontal and parietal white matter. Biochemical tests showed elevated liver transaminases, elevated serum very long chain fatty acids, and phytanic acid. After the death of the child at the age of 6 years, molecular diagnostics were continued in order to provide genetic counseling for his parents. Next generation sequencing (NGS) analysis with the TruSight One™ Sequencing Panel revealed a novel homozygous PEX6 p.Ala94Pro mutation. In silico prediction of variant severity suggested its possible benign effect. To conclude, in the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy together seem to be pathognomonic for ZS.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Mutação/genética , Síndrome de Zellweger/genética , Criança , Humanos , Masculino , FenótipoRESUMO
INTRODUCTION: Toxocarosis is a consequence of human infection by Toxocara canis larvae. There are symptomatic (visceral, ocular) and asymptomatic courses of toxocarosis. The cerebral form is very rare. CASE REPORT: We present a seven-year-old patient who developed a cerebral form of toxocarosis. She demonstrated focal neurological symptoms (epilepsy) confirmed by neuro-imaging and histopathological examinations. A positive test for toxocarosis essentially completed the other outcomes. On the basis of the clinical picture and the conducted tests a diagnosis of a cerebral form of toxocarosis was established. Mebendazole was applied in treatment.