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1.
Mov Disord ; 27(10): 1312-6, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22927201

RESUMO

No controlled studies exist regarding the pharmaceutical reduction of ataxia symptoms in ataxia telangiectasia (A-T). In a multicenter, double-blind, randomized, placebo-controlled crossover trial, oral betamethasone (BETA) and placebo were compared in terms of their reduction of ataxia symptoms as assessed with the International Cooperative Ataxia Rating Scale (ICARS). In this study of 13 A-T children, betamethasone reduced the ICARS total score by a median of 13 points in the intent-to-treat population and 16 points in the per-protocol population (ie, median percent decreases of ataxia symptoms of 28% and 31%, respectively). In conclusion, Oral betamethasone could be a promising therapy to relieve ataxia symptoms in A-T patients; however, long-term effectiveness and safety must be established. (Current Controlled Trials, number ISRCTN08774933.)


Assuntos
Anti-Inflamatórios/administração & dosagem , Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/fisiopatologia , Betametasona/administração & dosagem , Administração Oral , Adolescente , Ataxia Telangiectasia/diagnóstico , Criança , Feminino , Humanos , Masculino , Resultado do Tratamento
2.
NMR Biomed ; 23(4): 353-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20187168

RESUMO

Our aim was to compare urinary ethylmalonic acid (EMA) levels in subjects who had no apparent clinical reason to have increased levels of this substance but were suffering from non-specific CNS impairment, and healthy controls. Urinary EMA concentrations detected by (1)H-NMR spectroscopy were studied in 130 subjects with CNS impairment of unknown origin (with no definite diagnosis, no specific symptoms or signs, and normal common biochemical and metabolic screening results) and 130 age- and sex-matched healthy subjects. EMA levels exceeding two standard deviations (SD) above normal (i.e. 8.1 mmol/molCn) were found in a subgroup of CNS-impaired patients and healthy controls. EMA levels exceeding 2 SD above normal were fourfold prevalent in the urine of patients with non-specific CNS impairment compared to from the EMA levels in healthy controls. Moreover, we found that the level exceeding > 8.1 mmol/molCn (i.e. > + 2 SD) had sufficient discrimination accuracy in identifying subjects with non-specific CNS impairment; the level exceeding 12 mmol/molCn (i.e. > + 6 SD) reaches suitable accuracy (i.e. 100% specificity and 78.6% sensitivity). These observations are of importance, as we found that subtle increases in urinary EMA levels are frequent in patients with non-specific CNS impairment. The reasons for this association remain unknown.


Assuntos
Biomarcadores/urina , Encéfalo/fisiopatologia , Doenças do Sistema Nervoso Central/urina , Malonatos/urina , Adulto , Doenças do Sistema Nervoso Central/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Ressonância Magnética Nuclear Biomolecular , Adulto Jovem
3.
Clin Neurophysiol ; 121(5): 652-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20153689

RESUMO

OBJECTIVE: To assess the presence/absence of peculiar EEG features and epilepsy in MECP2-mutated Rett patients with the Zappella-Rett variant (Z-RTT) also known as preserved speech variant. METHODS: Retrospective analysis of 16 (age 19.4+/-8.4years; range 8-38years) MECP2 mutated Z-RTT cases, including 11 high or intermediate performance (HIP), and five low-performance (LP) patients was performed. Peculiar EEG features were analyzed as a function of the HIP or LP Z-RTT categories: (1) centro-temporal spikes, (2) multifocal EEG activity, (3) EEG encephalopathy (i.e. multifocal EEG activity associated with the presence of background slowing and diffuse slow activity), (4) spindles and K-complex. Furthermore, we assessed the occurrence of epilepsy. Correlations between electroclinical features and category of Z-RTT genotype (missense or truncation mutation) were also tested. RESULTS: The Z-RTT HIP group showed a very abnormal EEG (presence of centro-temporal spikes: p=0.004808), although the cases studied were not epileptogenic and did not develop encephalopathy. The LP group showed multifocal EEG activity (p=0.000229), EEG encephalopathy (p=0.000229) and epilepsy (p=0.299451). No significant differences between the prevalence of centro-temporal spikes, multifocal EEG activity, EEG encephalopathy, and epilepsy between the patients with the truncation or missense mutation were observed. CONCLUSIONS: EEG electrophysiological patterns and epileptogenic susceptibility differ in Z-RTT according to the level of performance (i.e. HIP or LP). SIGNIFICANCE: These results indicate that HIP and LP Z-RTT should be considered as distinct entities, not only on a clinical basis, but also as it concerns EEG features and epileptogenic susceptibility. These results could offer support in the practical management of patients and family counseling.


Assuntos
Eletroencefalografia , Epilepsia/etiologia , Variação Genética , Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Síndrome de Rett/complicações , Síndrome de Rett/genética , Adolescente , Adulto , Criança , Suscetibilidade a Doenças , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Genótipo , Humanos , Mutação de Sentido Incorreto , Estudos Retrospectivos , Síndrome de Rett/diagnóstico , Síndrome de Rett/fisiopatologia , Índice de Gravidade de Doença , Fala , Adulto Jovem
4.
J Child Neurol ; 25(1): 98-101, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19461121

RESUMO

For the first time, the use of urine [(1)H] magnetic resonance spectroscopy has allowed the detection of 1 case of guanidinoacetate methyl transferase in a database sample of 1500 pediatric patients with a diagnosis of central nervous system impairment of unknown origin. The urine [(1)H] magnetic resonance spectroscopy of a 9-year-old child, having severe epilepsy and nonprogressive mental and motor retardation with no apparent cause, revealed a possible guanidinoacetic acid increase. The definitive assignment of guanidinoacetic acid was checked by addition of pure substance to the urine sample and by measuring [(1)H]-[(1)H] correlation spectroscopy. Diagnosis of guanidinoacetate methyl transferase deficiency was further confirmed by liquid chromatography-mass spectrometry, brain [(1)H] magnetic resonance spectroscopy, and mutational analysis of the guanidinoacetate methyl transferase gene. The replacement therapy was promptly started and, after 1 year, the child was seizure free. We conclude that for this case, urine [(1)H] magnetic resonance spectroscopy screening was able to diagnose guanidinoacetate methyl transferase deficiency.


Assuntos
Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/urina , Guanidinoacetato N-Metiltransferase/deficiência , Encéfalo/metabolismo , Criança , Cromatografia Líquida , Análise Mutacional de DNA , Deficiências Nutricionais/terapia , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/terapia , Epilepsia/urina , Guanidinoacetato N-Metiltransferase/genética , Guanidinoacetato N-Metiltransferase/uso terapêutico , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/terapia , Deficiência Intelectual/urina , Espectroscopia de Ressonância Magnética/métodos , Masculino , Espectrometria de Massas , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/terapia , Transtornos dos Movimentos/urina , Prótons , Convulsões/diagnóstico , Convulsões/terapia , Convulsões/urina , Resultado do Tratamento
5.
Hum Mutat ; 30(12): 1667-75, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19810119

RESUMO

Autosomal recessive Ellis-van Creveld syndrome and autosomal dominant Weyer acrodental dysostosis are allelic conditions caused by mutations in EVC or EVC2. We performed a mutation screening study in 36 EvC cases and 3 cases of Weyer acrodental dysostosis, and identified pathogenic changes either in EVC or in EVC2 in all cases. We detected 40 independent EVC/EVC2 mutations of which 29 were novel changes in Ellis-van Creveld cases and 2 were novel mutations identified in Weyer pedigrees. Of interest one EvC patient had a T>G nucleotide substitution in intron 7 of EVC (c.940-150T>G), which creates a new donor splice site and results in the inclusion of a new exon. The T>G substitution is at nucleotide +5 of the novel 5' splice site. The three Weyer mutations occurred in the final exon of EVC2 (exon 22), suggesting that specific residues encoded by this exon are a key part of the protein. Using murine versions of EVC2 exon 22 mutations we demonstrate that the expression of a Weyer variant, but not the expression of a truncated protein that mimics an Ellis-van Creveld syndrome mutation, impairs Hedgehog signal transduction in NIH 3T3 cells in keeping with its dominant effect.


Assuntos
Disostoses/complicações , Disostoses/genética , Fibroblastos/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas de Membrana/genética , Mutação/genética , Transdução de Sinais , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Síndrome de Ellis-Van Creveld/complicações , Síndrome de Ellis-Van Creveld/genética , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Íntrons/genética , Masculino , Proteínas de Membrana/química , Camundongos , Dados de Sequência Molecular , Proteínas Mutantes/química , Células NIH 3T3 , Linhagem , Proteínas/química , Proteínas/genética
7.
NMR Biomed ; 22(5): 538-44, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19288536

RESUMO

In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using (1)H NMR spectroscopy. The urine 1D (1)H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC-MS/MS method and (1)H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in (1)H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that (1)H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency.


Assuntos
Líquidos Corporais/enzimologia , Guanidinoacetato N-Metiltransferase/deficiência , Espectroscopia de Ressonância Magnética/métodos , Prótons , Adulto , Criança , Pré-Escolar , Creatina/biossíntese , Feminino , Glicina/análogos & derivados , Glicina/sangue , Glicina/líquido cefalorraquidiano , Glicina/química , Glicina/urina , Humanos , Concentração de Íons de Hidrogênio , Lactente , Masculino , Valores de Referência
8.
Mol Pain ; 4: 51, 2008 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-18983665

RESUMO

BACKGROUND: Besides functioning as chemosensors for a broad range of endogenous and synthetic ligands, transient receptor potential vanilloid (TRPV) 1-4 channels have also been related to capsaicin (TRPV1), pain, and thermal stimuli perception, and itching sensation (TRPV1-4). While the expression of the TRPV1-4 genes has been adequately proved in skin, sensory fibres and keratinocytes, less is known about TRPV3 and TRPV4 expression in human blood cells. RESULTS: To study the gene expression of TRPV1-4 genes in human leukocytes, a quantitative Real-Time PCR (qRT-PCR) method, based on the calculation of their relative expression, has been developed and validated. The four commonly used house-keeping genes (HKGs), beta-Actin (Act-B), glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxanthine ribosyltransferase (HPRT1), and cyclophilin B (hCyPB), were tested for the stability of their expression in several human leukocyte samples, and used in the normalization procedure to determine the mRNA levels of the TRPV 1-4 genes in 30 healthy subjects. cDNAs belonging to all the TRPV1-4 genes were detected in leukocytes but the genes appear to be expressed at different levels. Our analysis did not show significant sex differences in TRPV1-4 cDNA levels in the 30 healthy subjects. The same qRT-PCR assay was used to compare TRPV1-4 expression between healthy controls and patients hyposensitive to capsaicin, pain and thermal stimuli: an almost doubled up-regulation of the TRPV1 gene was found in the pathological subjects. CONCLUSION: The qRT-PCR assay developed and tested in this study allowed us to determine the relative expression of TRPV1-4 genes in human leukocytes: TRPV3 is the least expressed gene of this pool, followed by TRPV4, TRPV1 and TRPV2. The comparison of TRPV1-4 gene expression between two groups of healthy and hyposensitive subjects highlighted the evident up-regulation of TRPV1, which was almost doubly expressed (1.9x normalized fold induction) in the latter group. All the four house-keeping genes tested in this work (Act-B, GAPDH, hCyPB, HPRT1) were classified as optimal controls and showed a constant expression in human leukocytes samples. We recommend the use of these genes in similar qRT-PCR studies on human blood cells.


Assuntos
Leucócitos/química , Limiar da Dor , Reação em Cadeia da Polimerase/métodos , Canais de Cátion TRPV/genética , Regulação para Cima/genética , Adolescente , Adulto , Idoso , Células Sanguíneas , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
9.
Clin Neurophysiol ; 119(11): 2455-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18842453

RESUMO

OBJECTIVE: To determine in MECP2-mutated Rett syndrome (RTT [MIM 312750]): (1) the prevalence of drug-resistant epilepsy (DRE); (2) whether the presence of DRE is related to the abnormal EEG patterns or to the particular MECP2 mutant genotype. METHODS: Retrospective survey of a large population of patients (n=154) evaluated between 1978 to 2007 (May) at the Child Psychiatry and Neurology Unit of Siena (Italy) with both clinical and genetic (i.e. MECP2 mutated) diagnoses of RTT. Some subjects were followed for up to 20 years. Among those, cases with epilepsy were first selected for study; within that group, cases with DRE were identified and studied. The association between clinical severity of their epilepsy and quantitative or qualitative scores of EEG severity was tested using rank coefficients (Spearman's rho values). The relationship between DRE and RTT genotype category (i.e. gene deletion, gene duplication, early truncating mutation, late truncating mutation, and missense mutation) or a specific MECP2 genotype was tested using the chi-square test. A p-value <0.05 (two sided) was considered to indicate statistical significance. RESULTS: Prevalence of DRE was 16% (i.e. 16 DRE out of 100 MECP2-mutated RTT epileptic patients). No significant relationship was found between clinical severity of DRE and quantitative (p=0.9190) or qualitative EEG scores (p=0.1511). In addition, no significant relationship was found between the DRE and the RTT genotype category (chi-square=1.147, DF=4, p=0.8867), or a specific MECP2 genotype (chi-square=30.958, DF=39, p=0.8173). CONCLUSIONS: Although RTT MECP2-mutated patients suffer from a serious and progressive encephalopathy, it is "epileptogenic" but not "DREgenic" as they have a decreased risk (16%) for DRE compared to the general epileptic population (DRE: 20-40%). The presence of DRE is not related to abnormal EEG findings or a particular MECP2 mutant genotype. SIGNIFICANCE: These observations could be of help in the practical management and family counseling.


Assuntos
Epilepsia/etiologia , Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Síndrome de Rett/complicações , Síndrome de Rett/genética , Adolescente , Adulto , Criança , Pré-Escolar , Resistência a Medicamentos , Eletroencefalografia/métodos , Epilepsia/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Fenótipo , Estudos Retrospectivos , Adulto Jovem
10.
Acta Paediatr ; 97(7): 952-4, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18430074

RESUMO

AIM: To assess the telomere length in apparently healthy obese and normal-weight subjects. METHODS: Seventy-six Caucasian subjects were chosen including 53 children (age 8.2+/-3.5 years) and 23 adults (age 40.5+/-8.4 years). Among these, 22 (12 children and 10 adults) were obese with a body mass index (BMI, kg/m2)>2 SD above the norm. Bioelectrical impedance analysis (BIA), measured with a multiple frequency analyzer, was used to estimate body composition. DNA extraction from white blood cells was used to estimate the telomere length by detection of terminal restriction fragments (TRF). RESULTS: No difference was found between the TRF lengths of obese and normal children. Obese adults had shorter TRF lengths than adults who were not obese (mean TRF length difference, -884.5; 95% confidence intervals -1727 to -41.8; t=2.183; df=17; p<0.041). CONCLUSIONS: Obese adults have shorter telomeres than their normal-weight counterparts, while this phenomenon is not present in childhood.


Assuntos
Obesidade/genética , Telômero/patologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Telômero/genética
11.
J Child Neurol ; 23(6): 683-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18182642

RESUMO

Five members from 3 generations, including a 35-year-old woman and her 2 sons, both mentally impaired to a different degree, were studied in a tertiary care hospital. Anamnestic, clinical, neurological, and radiological evaluations were used to describe phenotypes. A and B postaxial polydactyly, transmitted likely as autosomal dominant, was associated with an extensive variability of phenotypic features: (1) cutaneous syndactyly, (2) nail-teeth dysplasia, (3) osteopenia, and (4) mental delay. The likelihood that the constellation of observations we report here is caused by mutation of a single gene that subsequently affects multiple physiological activities, although fascinating, remains to be proven. Instead, we hypothesize that it likely develops as a contiguous gene syndrome.


Assuntos
Doenças Ósseas Metabólicas/genética , Displasia Ectodérmica/genética , Deficiência Intelectual/genética , Polidactilia/genética , Adolescente , Adulto , Idoso , Doenças Ósseas Metabólicas/diagnóstico , Criança , Aberrações Cromossômicas , Displasia Ectodérmica/diagnóstico , Feminino , Genes Dominantes/genética , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Unhas Malformadas/diagnóstico , Unhas Malformadas/genética , Linhagem , Fenótipo , Polidactilia/diagnóstico , Sindactilia/diagnóstico , Sindactilia/genética , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética
12.
Brain Dev ; 30(7): 461-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18226865

RESUMO

OBJECTIVE: Case study of a CNS impairment lacking in presumptive cause; case presents with a clinical phenotype encompassing multiple differently expressed and combined symptoms, as well as a subtle skin defect. MATERIALS AND METHODS: A 6-year-old male with apparently isolated mental delay, speech delay, attention deficit/hyperactivity disorder, epilepsy, and subtle and insignificant skin dyschromias. The patient underwent a systematic evaluation, including clinical history; medical, neurological and ophthalmologic examinations. Skin, teeth, nails, hair and sudation were examined for defects. Routine laboratory tests for blood, urine, were performed. The proband had thyroid function tests, electrocardiography, genitourinary system and abdominal examinations. Special examinations pertaining to mental performance, biochemistry, chromosome studies, imaging and electrodiagnostic studies, and skin biopsy were also performed. RESULTS: Investigators ruled out genetic syndromes, congenital infections, fetal deprivation, perinatal insults, intrauterine exposure to drug abuse, and postnatal events such as CNS infections as possible common causes of brain impairment. Being all further test negative, the patient exhibited an ultrastructural defect of the skin, identical to that previously described [Buoni S, Zannolli R, de Santi MM, Macucci F, Hayek J, Orsi A et al. Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vesicular trafficking and melanosome defects. Eur J Neurol 2006;13:842-51], suggesting that some cell compartments, such as rough endoplasmic reticulum, lysosomes, Golgi apparatus, and the vesicular zone (racket) of Birbeck granules, sharing similar components, can be altered, resulting in a common defect in cell trafficking, associated to melanosome defects. CONCLUSIONS: This new devasting, ultrastructural phenotype accompanied by apparently unspecific and mixed neurological symptoms should represent a future challenge to finally discover the pathogenesis of many childhood CNS symptoms, that currently seem to lack any apparent cause.


Assuntos
Melanócitos/ultraestrutura , Melanossomas/ultraestrutura , Síndromes Neurocutâneas/patologia , Biópsia/métodos , Criança , Humanos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Microscopia Eletrônica de Transmissão , Síndromes Neurocutâneas/metabolismo , Síndromes Neurocutâneas/fisiopatologia , Organelas/metabolismo , Organelas/ultraestrutura , Pele/metabolismo , Pele/patologia , Pele/ultraestrutura
13.
Brain Dev ; 30(1): 53-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17583458

RESUMO

To investigate the clinical picture, the neurophysiological pattern, and neuropathological features of a young woman with severe drug-resistant epilepsy of unknown cause. We used the patient's clinical records from the age of 2 to 20years including neurophysiological patterns recorded via both scalp and cortex electrodes and results of studies conducted on the brain neuropathological specimen. The patient, with severe mental/psychomotor retardation, suffered from severe epilepsy from an early age, characterized by daily seizures of multiple types (atypical absences, tonic, and complex partial seizures), high frequency, and intractability. The neurophysiological pattern indicated multiple independent spike foci (SE-MISF). When she was 16, a vagal nerve stimulator was implanted without success. Neither neuroimaging (brain MRI and ictal SPECT) nor surface EEGs identified unique loci of seizure onset, establishing her as a candidate for a complete callosotomy. When the patient was 19, before the callosotomy, invasive EEG (i.e., electrocorticography) using just a few electrodes in different lobes showed the presence of a distinctive pattern. The surgical specimen, taken very close to one of the activity sites, showed architectural abnormalities and neurons that were giant or immature but not dysmorphic, indicative of focal cortical dysplasia (FCD) type 1b. Twelve months after the callosotomy, according to the Engel score, the patient exhibited a large improvement in quality of life, without permanent complications from the interhemispheric disconnection. (1) Hidden FCD type 1b could represent a missing diagnosis in patients with SE-MISF in the absence of other causes for their seizures. (2) Complete callosotomy can be efficacious in patients with SE-MISF with hidden FCD type 1b.


Assuntos
Córtex Cerebral/anormalidades , Córtex Cerebral/fisiopatologia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/fisiopatologia , Potenciais de Ação/fisiologia , Adulto , Córtex Cerebral/patologia , Corpo Caloso/cirurgia , Denervação , Erros de Diagnóstico/prevenção & controle , Eletrodiagnóstico , Eletroencefalografia , Epilepsia/patologia , Potenciais Evocados/fisiologia , Feminino , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/patologia , Deficiência Intelectual/fisiopatologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Neurônios/patologia , Procedimentos Neurocirúrgicos , Valor Preditivo dos Testes , Qualidade de Vida , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
14.
Pediatr Dermatol ; 24(3): 267-71, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17542878

RESUMO

We report a 6-year-old girl with a subtle form of hypohidrotic ectodermal dysplasia and a phenotype consisting of curly hair, a round face, a stocky build, and obesity, which was associated with intrathoracic neuroblastoma. Although this new association could be a chance occurrence, its description may alert physicians to look for similar combinations and report these, as it may lead to better syndrome delineation, and patient care.


Assuntos
Displasia Ectodérmica/diagnóstico , Neuroblastoma/complicações , Criança , Displasia Ectodérmica/complicações , Feminino , Febre de Causa Desconhecida/complicações , Cabelo/anormalidades , Humanos , Obesidade/complicações , Glândulas Sudoríparas/anormalidades , Neoplasias Torácicas/complicações , Anormalidades Dentárias
15.
Brain Dev ; 29(1): 51-4, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16919904

RESUMO

Peroxisomal disorders appear with a frequency of about 1:5000 in newborns. Peroxisomal D-bifunctional protein (D-BP), encoded by the HSD17B4 gene (gene ID: 3294; locus tag: HGNC:5213, chromosome 5q2; official symbol: HSD17B4; name: hydroxysteroid (17-beta) dehydrogenase; gene type: protein coding) (OMIM *601860), comprises an 80 kDa multifunctional enzyme involved in peroxisomal beta-oxidation of certain fatty acids and the synthesis of bile acids. Its deficiency causes a very severe, Zellweger-like clinical phenotype and most patients die within the first year of life. In this paper, we report a case of D-BP deficiency in a patient with two heterozygous trinucleotide deletions (233_235 del AAG and 824_826 del AGA) in the HSD17B4 gene. The patient suffered from a peculiar epileptic phenotype (i.e. a West syndrome with a "modified hypsarrhythmic pattern"--Hrachovy et al. Epilepsia 1984;25:317-25), clinically appearing as drug-resistant asymmetric spasms. Vigabatrin seemed the most effective among the antiepileptic drugs. The patient died at the age of 23 months owing to respiratory complications. To date, only a few patients with D-BP deficiency have been described in the literature. This case adds to our knowledge of the clinical presentation of bifunctional protein deficiency.


Assuntos
17-Hidroxiesteroide Desidrogenases/deficiência , 17-Hidroxiesteroide Desidrogenases/genética , Resistência a Medicamentos/genética , Predisposição Genética para Doença/genética , Hidroliases/deficiência , Hidroliases/genética , Espasmos Infantis/enzimologia , Espasmos Infantis/genética , Anticonvulsivantes/uso terapêutico , Análise Mutacional de DNA , Progressão da Doença , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/enzimologia , Epilepsia/genética , Evolução Fatal , Deleção de Genes , Marcadores Genéticos/genética , Humanos , Lactente , Masculino , Mutação/genética , Proteína Multifuncional do Peroxissomo-2 , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico
16.
Brain Dev ; 29(6): 373-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17174051

RESUMO

We report a unique combination of symptoms in a case of Kabuki syndrome (KS), a multiple malformation/mental retardation syndrome that has a prevalence of 1:32,000 to 1:86,000. The patient was a mentally delayed 12-year-old male with trichrome vitiligo, ectodermal defect, and hypogammaglobulinemia A and G. This unique combination of signs, described here for the first time, indicates that KS comprises multiple deficits that affect not only the brain, but ectoderm-derived structures and the immune system as well. Our report may provide important clues for understanding the pathogenesis of the KS.


Assuntos
Anormalidades Múltiplas/fisiopatologia , Agamaglobulinemia/complicações , Displasia Ectodérmica/complicações , Deficiência de IgA , Deficiência de IgG , Deficiência Intelectual/complicações , Vitiligo/complicações , Anormalidades Múltiplas/patologia , Criança , Humanos , Deficiência Intelectual/patologia , Masculino , Vitiligo/patologia
17.
Arch Neurol ; 63(10): 1479-82, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17030666

RESUMO

BACKGROUND: To our knowledge, there have been no reports on the control of central nervous system symptoms in patients with ataxia-telangiectasia. OBJECTIVE: To preliminarily determine the effectiveness of corticosteroid therapy on the central nervous system symptoms of a child with ataxia-telangiectasia in whom neurological signs improved when, occasionally, he was given betamethasone to treat asthmatic bronchitis attacks. DESIGN: Case report. SETTING: Tertiary care hospital. Patient A 3-year-old boy with the classic hallmarks and a proved molecular diagnosis of ataxia-telangiectasia. INTERVENTIONS: We used betamethasone, 0.1 mg/kg per 24 hours, divided every 12 hours, for 4 weeks to preliminarily determine its effectiveness on the child's central nervous system symptoms and its safety. Methylprednisolone, 2 mg/kg per 24 hours, divided every 12 hours, was then given in an attempt to perform a long-term treatment. RESULTS: There were improvements in the child's neurological symptoms 2 or 3 days after the beginning of the drug treatment. After 2 weeks of treatment, the improvement was dramatic: the disturbance of stance and gait was clearly reduced, and the control of the head and neck had increased, as had control of skilled movements. At 4 weeks of treatment, adverse effects mainly included increased appetite and body weight and moon face. No beneficial effect was obtained when, after 4 weeks, betamethasone was replaced with methylprednisolone. Six months later, without therapy, the child continued to experience severe signs of central nervous system impairment. CONCLUSION: Controlled studies to better understand the most appropriate drug and therapeutic schedule are required.


Assuntos
Ataxia Telangiectasia/tratamento farmacológico , Betametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Ataxia/tratamento farmacológico , Ataxia/etiologia , Ataxia/fisiopatologia , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/fisiopatologia , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/fisiopatologia , Pré-Escolar , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Túnica Conjuntiva/fisiopatologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Esquema de Medicação , Quimioterapia Combinada , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Metilprednisolona/administração & dosagem , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
18.
J Child Neurol ; 21(6): 531-3, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16948942

RESUMO

Familial reports of a robertsonian translocation in more than two generations are rare. We report three generations (a daughter, the mother, and the mother's father) with a heterozygous, balanced robertsonian translocation t(13;14)(q11;q11). Central nervous system disease was present, but differentially expressed, in generations I and III. The daughter presented with mental delay and epilepsy, and the mother was apparently healthy, whereas the mother's father was again symptomatic, with borderline intelligence. Fluorescent in situ hybridization analysis was performed to exclude a loss or gain of chromosomal material. No uniparental disomy was present. We concluded that genetic counseling in the presence of this rearrangement was extremely difficult, independent of the affected parent being symptomatic or asymptomatic.


Assuntos
Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 14/genética , Epilepsia/genética , Deficiência Intelectual/genética , Translocação Genética/genética , Adulto , Criança , Feminino , Humanos , Masculino , Linhagem
19.
Brain Dev ; 28(6): 410-2, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16504444

RESUMO

Vertigo in children is relatively under examined in the literature. Among its causes, vestibular neuritis (VN) represents only 2% of cases, with its etiology remaining unknown. We report for the first time a 4-year-old boy with vestibular neuritis and serological results compatible with adenoviral infection. Serological diagnosis was performed on the basis of a rise and consequent normalization of complement fixation (CF) titers of the plasma antibodies. Although we were not able to detect exactly when the infection started, we were able to detect an increased level of adenovirus antibodies by CF titers, followed by a decrease (i.e. 1/16, then 1/8, then <1/4) during the recovery. This is typical of a resolving infection. Furthermore, that this increase in antibodies was specific to an adenovirus infection was suggested by the observation that we did not detect increases in antibodies to other common viruses (i.e. herpes simplex and zoster viruses, Epstein-Barr virus, cytomegalovirus, influenza and parainfluenza viruses). This allows us to exclude the chance of nonspecific antibody activation. We concluded that, although our data do not formally demonstrate an involvement of adenovirus in VN, they suggest such an involvement. This may be of interest, given that a viral etiology for VN has been proposed but not definitively proven.


Assuntos
Adenoviridae/imunologia , Infecções por Adenovirus Humanos/complicações , Neuronite Vestibular/virologia , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/imunologia , Anticorpos Antivirais/sangue , Pré-Escolar , Humanos , Masculino
20.
Clin Neurophysiol ; 117(5): 959-63, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16545599

RESUMO

OBJECTIVE: To study the outcome of EEG from patients with Chiari I malformations and nonspecific EEG abnormalities, after posterior fossa decompression and CSF flow normalization. METHODS: Three 'apparently asymptomatic' children who had been diagnosed with Arnold-Chiari type 1 EEG abnormalities and who exhibited (a) a wide range of abnormalities according to common anatomical Chiari MRI classifications (Elster AD, Chen MY. Chiari I malformations: clinical and radiologic reappraisal. Radiology 1992;183:347-53), (b) a lack of specific, clinical signs of increased intracranial pressure, and (c) apparently unrelated, EEG-nonspecific abnormalities (focal intermittent rhythmic delta activity (IRDA)--solely in patients 1 and 3, and with focal IRDA plus spikes and spike waves of high voltage in patient 2). Standard EEGs were recorded before surgery and within one month of surgery, which was performed in conjunction with intraoperative echo-Doppler ultrasonography to control CSF flow. Subsequent EEGs and clinical follow-ups were performed within 6-12 months of surgery. RESULTS: In all patients, intraoperative echo-Doppler ultrasonographic control demonstrated poor CSF flow, which was completely restored by posterior fossa decompression. In all patients, the EEG abnormalities disappeared within one month of surgery and the EEGs were normal at follow-up. CONCLUSIONS: A new CNS symptom, identified as focal IRDA alone or focal IRDA plus spikes and spike waves of high voltage in the EEG, seems to be associated with poor CSF flow in 'apparently asymptomatic' patients with Chiari type I malformations. SIGNIFICANCE: The identified, paroxysmal EEG abnormalities should be interpreted as an indirect sign of subtle CNS distress.


Assuntos
Malformação de Arnold-Chiari , Pressão do Líquido Cefalorraquidiano/fisiologia , Descompressão Cirúrgica , Eletroencefalografia , Adolescente , Malformação de Arnold-Chiari/líquido cefalorraquidiano , Malformação de Arnold-Chiari/fisiopatologia , Malformação de Arnold-Chiari/cirurgia , Criança , Feminino , Forame Magno/patologia , Forame Magno/cirurgia , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino
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