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1.
Medicine (Baltimore) ; 98(44): e17838, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689873

RESUMO

RATIONALE: Recurrence of Klinefelter syndrome (KS) in non-twin brothers is very rare. This study examined the inheritance pattern of supernumerary X chromosomes in non-twin brothers. PATIENT CONCERNS: A 16-year-old man presented with small-sized testicles. During his diagnostic work-up, his brother, in his late 20's, also complained of small testes and erectile dysfunction. DIAGNOSIS: Chromosome analysis in peripheral blood revealed non-mosaic 47,XXY karyotype in both brothers. Their mother showed a normal 46,XX karyotype. INTERVENTIONS: To examine the inheritance pattern of supernumerary X chromosomes, quantitative-fluorescence PCR was performed with small tandem repeat markers. It revealed that their supernumerary X chromosomes were inherited from different parents. OUTCOMES: After the diagnosis of KS, 2 brothers started to receive testosterone treatment. CONCLUSION: This case report is the first to report differences in the origins of supernumerary X chromosomes in brothers with KS and furthers the current understanding of the cytogenetic mechanisms in KS.


Assuntos
Cromossomos Humanos X , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Adolescente , Adulto , Disfunção Erétil/etiologia , Humanos , Síndrome de Klinefelter/tratamento farmacológico , Masculino , Pais , Reação em Cadeia da Polimerase/métodos , Irmãos , Sequências de Repetição em Tandem , Testosterona/uso terapêutico
2.
J Forensic Odontostomatol ; 37(2): 9-17, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589591

RESUMO

The study aimed to carry out a comparative analysis between the lip print patterns in individuals with Down Syndrome and their nonsyndromic biological siblings. This was a cross-sectional blind study using an inductive approach and extensive direct observation procedures. A total of 68 cheiloscopic charts, named cheilograms, were divided into two groups (n=34), as follows: G1, including Down Syndrome individuals; and G2, including their nonsyndromic siblinggs. The convenience sample was selected in the city of João Pessoa, PB, Brazil. The following features were evaluated in eight labial regions called sub-quadrants: oral commissures (downturned, horizontal and upturned); lip thickness (thin, medium, thick and mixed); and labial grooves (I - complete vertical; I '- incomplete vertical; II - bifurcated; III - criss-cross; IV - reticular; or V - undefined). The data were analyzed by paired Student's t test and McNemar's Chi-square, with a 5% significance level. Most Down Syndrome individuals were found to have downturned oral commissures in 73.5% of cases, while their siblings showed a predominance of horizontal commissures in 73.5% of cases (p=0.009). There was no statistically significant difference for lip thickness between groups. In the analysis of labial groove patterns, Down Syndrome individuals (G1) showed a significant prevalence of the type I pattern (52.2%) as compared to their nonsyndromic siblings (30.1%) (p =< 0.001). Due to the tendency of having vertical labial groove patterns and downturned commissures, Down Syndrome individuals present cheiloscopic differences in relation to their nonsyndromic biological siblings, which suggests that syndromic genetics influences the development of these features. However, this may imply in a reduced potential of cheiloscopic identification due to the low divergence of labial phenotypes among Down Syndrome individuals.


Assuntos
Síndrome de Down , Irmãos , Brasil , Estudos Transversais , Humanos , Lábio
3.
BMJ ; 367: l5784, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645334

RESUMO

OBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.


Assuntos
Infecções Bacterianas/epidemiologia , Suscetibilidade a Doenças/imunologia , Transtornos de Estresse Traumático/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Anamnese , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Irmãos , Transtornos de Estresse Traumático/imunologia , Taxa de Sobrevida , Suécia/epidemiologia , Adulto Jovem
5.
Psychiatr Danub ; 31(Suppl 3): 227-230, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488731

RESUMO

Today, the concepts of health and illness require a global vision of man; the suffering of the person places the entire environment in great difficulty: health professionals, family, society. It is important not to simplify the response to a purely health-focused view of the disorder, because fragile people possess a deep need to feel welcomed, listened to, understood and accepted. Service provision that is respectful of the dignity of the person is an important challenge both for those who are responsible for providing services to individuals and their families as well as for the entire community. Therefore in providing care the human qualities of the health professional and not only his technical skills come into play: blending together science and humanitarian ethos. The provision of care therefore "forces" us to broaden our horizons and requires us to face the challenge of responsibility towards the Other, the human condition of being-for. However, ethical capacity cannot be born solely out of sharing standards or adhering to regulations and respecting prohibitions: it stems from high and unconditional moral values and meanings. The ME-YOU relationship represents the primary ethical factor of the human being: my responsibility towards the Other is unconditional. In the book of Genesis when the Lord asks Cain: "... where is Abel, your brother?" He responds with another question: "Am I my brother's keeper?" In this biblical passage Cain kills Abel: the rejection of brotherhood and the care of the other only leads to the death of the Other. "Where is your brother?" This question is crucial in today's day and age and must be taken seriously: it is the decisive question that forces us to decide how to place ourselves in relationship with the other and with the world: do we choose proximity or distance, connection or indifference?


Assuntos
Cuidadores/ética , Cuidadores/psicologia , Transtornos Mentais/psicologia , Princípios Morais , Comportamento Social , Saúde , Humanos , Masculino , Irmãos/psicologia , Mudança Social
6.
Medicine (Baltimore) ; 98(33): e16899, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415434

RESUMO

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive multisystem disorder characterized by oculocutaneous albinism (OCA) and bleeding diathesis, although it displays both genetic and phenotypic heterogeneity. Several genetic subtypes of HPS have been identified in human; however, the characterizations of HPS type 4 (HPS-4) genotype and phenotype remain unclear. This study was aimed to identify gene mutation responsible for HPS-4 with pulmonary fibrosis (PF).Two Chinese siblings in their 50 s afflicted with OCA and progressive dyspnea were recruited and underwent clinical and genetic examinations. In both patients, chest high-resolution computerized tomography showed severe interstitial PF in bilateral lung fields, and the pulmonary function test indicated restrictive lung disease. A novel homozygous frameshift mutation (NM_022081: c.630dupC; p.A211fs) in the HPS4 gene was identified by whole-exome sequencing analysis followed by Sanger DNA sequencing, and it segregated with the phenotypes. The c.630dupC mutation was not found in unaffected healthy controls. The patients were considered as HPS-4 with interstitial PF and eventually died of respiratory failure.This is the first report on the genotype and clinical phenotype of HPS-4 in China. Our results demonstrate the association between a novel frameshift mutation in HPS4 and severe PF with poor prognosis in HPS is presented.


Assuntos
Mutação da Fase de Leitura , Síndrome de Hermanski-Pudlak/genética , Fibrose Pulmonar Idiopática/genética , Proteínas/genética , Adulto , China , Testes Genéticos , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA , Irmãos
7.
Res Nurs Health ; 42(5): 334-348, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31418465

RESUMO

Well siblings of chronically ill children experience family disruptions that profoundly affect them. Previous research focusing on well siblings' experiences has often produced inconsistent findings, likely the result of varying study designs and samples. The purposes of this synthesis research study were twofold: (a) to assess the applicability of existing grounded theory of sibling response to a child's cancer to a wider range of childhood conditions; and (b) to refine the existing theory to reflect the experiences of the broader sample. Data for the synthesis came from a National Institute of Nursing Research-funded mixed-methods synthesis examining the intersection of childhood chronic illness and family life. The current analysis was based on well sibling results extracted from 78 research reports published between 2000 and 2014. An existing grounded theory, Creating a Tenuous Balance (CTB), was discovered at the outset of analysis and used as the primary framework for coding and synthesizing results. The focus of most studies was siblings' responses to 14 chronic conditions, with cancer being the most often studied. Results reflected siblings' perspectives of their experiences as well as perspectives of parents and the ill child. The analysis substantiated all four patterns of sibling behavior included in CTB, with the patterns of adapting to changes in personal and family life, and handling strong emotions being especially challenging aspects of the sibling experience. Moreover, the results expanded several aspects of CTB. The analysis provided evidence of the applicability of the theory to a varied group of chronic conditions and enabled us to identify important areas for developing interventions to support siblings.


Assuntos
Adaptação Psicológica , Doença Crônica/psicologia , Crianças com Deficiência/psicologia , Voluntários Saudáveis/psicologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Irmãos/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino
8.
Harefuah ; 158(8): 540-544, 2019 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-31407545

RESUMO

INTRODUCTION: Many Jewish doctors in the Holocaust - in ghettos, concentration and extermination camps and in the forests - displayed courage, valor and sacrifice in the resistance front against the Nazis and their allies. The scope of their actions was broad: active resistance in the underground and rebellion movements or in the lines of partisans in the forests; hiding and saving Jews; smuggling medicines; preparing false medical records; secretly conducting surgery and other treatments; refusing the demands to submit lists of patients and workers, thus sentencing them to death; staying by the sick and the needy in the ghettos, even when they could escape, and many more. All this was done out of truth to their conscience, sometimes even beyond their commitment to the doctor's oath, placing themselves in uncertain situations, in distress, hunger, oppression and humiliation, risking their own lives and those of their families. It is admirable how those degrees of courage, bravery, willpower and sacrifice could develop out of such terrible physical and mental distress. The resistance was an extensive wide-ranging occurrence among the Jewish doctors and not one of just a few individuals. This article presents a number of examples of diverse forms of resistance, of individuals as well as of groups of physicians.


Assuntos
Holocausto , Judeus , Socialismo Nacional , Humanos , Judaísmo , Masculino , Irmãos
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(6): 460-466, 2019 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-31340617

RESUMO

Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions: The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Antígenos HLA , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Doadores não Relacionados
10.
Pan Afr Med J ; 32: 179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312293

RESUMO

Introduction: Early diagnosis and treatment of paediatric HIV is key as mortality of untreated patients is very high in the first two years of life, and reaches 80% by four years. Case finding efforts for children especially outside Prevention of mother-to-child transmission (PMTCT) is inadequate. Targeting siblings of index HIV-exposed and infected children is an important way of improving identification and enrolment into care thereby reducing paediatric mortality. The study therefore aimed to determine the prevalence of HIV infection among siblings of HIV positive children in care in Calabar. Methods: This descriptive cross-sectional study was conducted among children aged six weeks to 15 years who are siblings of HIV positive children receiving care. Parental consent and child assent were obtained, the children were tested for HIV at their homes irrespective of their prior test results. Ethical clearance certificates were obtained from the health institutions. Results: Siblings of 401 index patients were tested for HIV, four were positive giving a prevalence rate of 1%. Three hundred and sixty-seven 367(91.5%) had been tested previously while 34(8.5%) never had HIV test. Among the siblings who were HIV positive, 1(0.3%) was a male while 3(0.7%) were females. There were more HIV positive siblings in the 11-15 years age group. Conclusion: All the four HIV positive siblings were from the lower socioeconomic class (p=0.022). The routine screening of siblings of HIV positive children should be sustained with focus on adolescents from the lower socioeconomic class. This will improve early identification and enrolment into care thereby reducing paediatric mortality.


Assuntos
Infecções por HIV/epidemiologia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Programas de Rastreamento/métodos , Irmãos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Nigéria/epidemiologia , Prevalência
11.
Nat Commun ; 10(1): 3018, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289270

RESUMO

The analysis of whole-genome sequencing studies is challenging due to the large number of noncoding rare variants, our limited understanding of their functional effects, and the lack of natural units for testing. Here we propose a scan statistic framework, WGScan, to simultaneously detect the existence, and estimate the locations of association signals at genome-wide scale. WGScan can analytically estimate the significance threshold for a whole-genome scan; utilize summary statistics for a meta-analysis; incorporate functional annotations for enhanced discoveries in noncoding regions; and enable enrichment analyses using genome-wide summary statistics. Based on the analysis of whole genomes of 1,786 phenotypically discordant sibling pairs from the Simons Simplex Collection study for autism spectrum disorders, we derive genome-wide significance thresholds for whole genome sequencing studies and detect significant enrichments of regions showing associations with autism in promoter regions, functional categories related to autism, and enhancers predicted to regulate expression of autism associated genes.


Assuntos
Transtorno do Espectro Autista/genética , Análise de Dados , Genoma Humano/genética , Modelos Genéticos , Algoritmos , Conjuntos de Dados como Assunto , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Irmãos , Sequenciamento Completo do Genoma/métodos
13.
Fa Yi Xue Za Zhi ; 35(3): 319-323, 2019 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31282628

RESUMO

Abstract: Objective To investigate the application of the comprehensive use of multiple genetic markers in full and half sibling relationship testing through the identification of a case of suspected sibling relationship. Methods Genomic DNA were extracted from bloodstain samples from 4 subjects (ZHANG-1, ZHANG-2, male; ZHANG-3, ZHANG-4, female). Autosomal STR loci, X-STR, Y-STR loci and polymorphisms of mtDNA HV-Ⅰ and Ⅱwere genotyped by EX20 STR kit, X19 kit, Data Y24 STR kit, and Sanger sequencing, respectively. Results According to autosomal STR based IBS scoring results, full sibling relationships were indicated among ZHANG-2, ZHANG-3 and ZHANG-4, but those were not indicated between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4. According to autosomal STR based FSI and HSI, with ITO method and discriminant function method, full sibling relationships among ZHANG-2, ZHANG-3 and ZHANG-4 were indicated, and half sibling relationships between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4 were also indicated. X-STR and mtDNA sequencing results showed that all the 4 samples came from a same maternal line, and Y-STR results showed that ZHANG-1 and ZHANG-2 did not come from a same paternal line, which supported the half sibling relationship between ZHANG-1 and ZHANG-2 or ZHANG-3 or ZHANG-4, verified by parental genotype reconstruction based on autosomal STR genotyping. Conclusion For the identification of sibling relationships, it is effective to have reliable results with the mutual verification and support of multiple genetic markers (autosomal STR, sex chromosomal STR and mtDNA sequence) and calculations (IBS, ITO, discriminant function method and family reconstruction).


Assuntos
Genética Forense , Irmãos , Alelos , Cromossomos Humanos Y , Impressões Digitais de DNA , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Repetições de Microssatélites
15.
Ann Hematol ; 98(9): 2163-2177, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243569

RESUMO

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Herpesvirus Humano 4/metabolismo , Transtornos Linfoproliferativos , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Humanos , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Irmãos , Taxa de Sobrevida
16.
BMC Neurol ; 19(1): 122, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185936

RESUMO

BACKGROUND: Krabbe disease (also known as globoid cell leukodystrophy) cause by a deficiency of the enzyme ß-galactocerebrosidase (galactosylceramidase, GALC). The deficiency of GALC leads to accumulation of galactosylceramide and psychosine, the latter GALC substrate having a potential role in triggering demyelination. Typically, the disease has an infantile onset, with rapid deterioration in the first few months, leading to death before the age of 2 years. The late onset forms (late-infantile, juvenile, and adult forms) are rare with variable clinical outcomes, presenting spastic paraplegia as the main symptom. CASE PRESENTATION: We recruited a family with two affected individuals. The proband (Patient 1), a 25-year-old male, was presented with slow progressive symptoms, including spastic gait disturbance and vision loss since the 5th year of life. His elder sister (Patient 2), became wheelchair-bound and demented at the age of 22 years. Brain magnetic resonance imaging (MRI) showed increased signal intensity in the white matter along with the involvement of the bilateral corticospinal tracts. GALC deficiency was confirmed by biochemical analysis. DNA sequencing revealed two mutations (c.865G > C: p. G289R and c.136G > T: p. D46Y) in GALC. The clinical characteristics, brain MRI, biochemical and molecular findings led to the diagnosis of Krabbe disease. CONCLUSION: Clinical and neuroimaged signs, positive enzymatic analysis and molecular data converged to definite diagnosis in this neurodegenerative disease.


Assuntos
Galactosilceramidase/deficiência , Galactosilceramidase/genética , Leucodistrofia de Células Globoides/genética , Adulto , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Linhagem , Irmãos , Adulto Jovem
17.
Medicine (Baltimore) ; 98(23): e15908, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31169704

RESUMO

RATIONALE: Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome is a very rare multisystem disorder, which shows malformations of the central nervous system, ears, eyes, teeth, and skeleton that was first reported in 1991. Only a few cases that sporadically occurred have been reported worldwide. The research investigating the pathogenesis and patterns of CODAS inheritance is still ongoing. There is no satisfactory treatment for this rare genetic disease yet. Due to the lack of curative medical treatment, rehabilitation could play a major role in treatment for genetic disease. PATIENT CONCERNS: To our best knowledge, the 2 children described in this study are the only CODAS syndromes siblings reported in the world so far. These Korean siblings show highly distinctive features consisting of developmental delay, cataracts, vulnerability to tooth decay, epiphyseal dysplasia, and anomalous ears. DIAGNOSES: CODAS syndrome. INTERVENTIONS: Comprehensive long-term rehabilitation treatment during 5 years. OUTCOMES: We report on the progress of the comprehensive long-term rehabilitation treatment at 5-year follow-up. Their fine motor and language skills development improved similarly to that of same-aged children. We observed the positive effect of rehabilitation on the quality of life. LESSONS: The therapy of genetic disorders is challenging for pediatric neurologists and pediatric physiatrists. We suggest that rehabilitation is the best treatment currently available for this genetic disease that yields satisfactory therapeutic effect.


Assuntos
Anormalidades Craniofaciais/patologia , Anormalidades Craniofaciais/reabilitação , Anormalidades do Olho/patologia , Anormalidades do Olho/reabilitação , Transtornos do Crescimento/patologia , Transtornos do Crescimento/reabilitação , Luxação Congênita de Quadril/patologia , Luxação Congênita de Quadril/reabilitação , Osteocondrodisplasias/patologia , Osteocondrodisplasias/reabilitação , Irmãos , Anormalidades Dentárias/patologia , Anormalidades Dentárias/reabilitação , Criança , Feminino , Humanos , Masculino , Qualidade de Vida , República da Coreia
18.
Int Arch Allergy Immunol ; 180(1): 37-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31207596

RESUMO

BACKGROUND: Increasing evidence suggests a positive association between attention-deficit hyperactivity disorder (ADHD) and atopic diseases. However, the risk of atopic diseases in unaffected siblings of patients with ADHD has not been investigated. OBJECTIVE: To investigate the risk of developing atopic diseases among unaffected siblings of ADHD probands. METHODS: Using data from the Taiwan National Health Insurance Research Database, 20,170 unaffected siblings of patients with ADHD born between 1980 and 2000 and 80,680 age-, birth time-, and residence-matchedcontrols were included in this study. Diagnoses of atopic diseases, including asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis, were ascertained from 1996 or the birth time until the end of 2011. RESULTS: Breslow-Cox proportional hazard regression analyses with adjustment for demographic data showed that compared with the controls, unaffected siblings of patients with ADHD had a higher risk of developing asthma (relative risk [RR], 1.19; 95% confidence interval [CI], 1.15-1.24), atopic dermatitis (RR, 1.10; 95% CI, 1.04-1.16), allergic rhinitis (RR, 1.17; 95% CI, 1.14-1.21), allergic conjunctivitis (RR, 1.13; 95% CI, 1.09-1.17), and any of these atopic diseases (RR, 1.13; 95% CI, 1.10-1.15). CONCLUSION: The unaffected siblings of ADHD probands were more likely to develop atopic diseases compared with the controls, suggesting shared risk factors for both diseases.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/epidemiologia , Irmãos , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Vigilância da População , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
19.
Zhonghua Xue Ye Xue Za Zhi ; 40(4): 294-300, 2019 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-31104440

RESUMO

Objective: To compare the clinical efficacy of umbilical cord blood transplantation (UCBT) and hematopoietic stem cell transplantation from HLA-matched sibling donors (MSD-HSCT) in the treatment of myelodysplastic syndrome-EB (MDS-EB) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) . Methods: A cohort of 64 patients (including 38 cases of MDS-EB and 26 cases of AML-MRC) who received UCBT/MSD-HSCT from February 2011 to December 2017 were retrospectively analyzed. Results: ①Compared with MSD-HSCT group, UCBT group had a higher proportion of AML-MRC patients [52.8% (19/36) vs 25.0% (7/28) , P=0.025], and a lower median age [13 (1.5-52) years vs 32 (10-57) years, P=0.001]. ②The engraftment of neutrophils both in UCBT and MSD-HSCT groups on +42 d was 100%, and the median engraftment time was 17.5 (11-31) d and 11.5 (10-20) d, respectively. The engraftment of platelet at +100 d in UCBT group was 91.4%, the median engraftment time was 40 (15-96) d; The engraftment of platelet at +100 d in MSD-HSCT group was 100%, and the median engraftment time was 15 (11-43) d. ③There were no statistically significant differences in terms of the cumulative incidence of Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD of 100 d and transplant related mortality (TRM) of 180 d, relapse rate, overall survival (OS) , disease-free survival (DFS) between UCBT and MSD-HSCT groups (P>0.05) . ④The 3-year cumulative incidence of chronic GVHD (cGVHD) and severe chronic GVHD in UCBT group were lower than of MSD-HSCT group [28.3% (95%CI 13.4%-45.3%) vs 67.9% (95%CI 46.1%-82.4%) , P=0.002; 10.3% (95%CI 2.5%-24.8%) vs 50.0% (95%CI 30.0%-67.1%) , respectively, P<0.001]. The cumulative 3-year incidence of GVHD-free and relapse-free survival (GRFS) of UCBT group was significantly higher than of MSD-HSCT group [55.0% (95%CI 36.0%-70.6%) vs 28.6% (95%CI 13.5%-45.6%) , P=0.038]. Conclusion: UCBT could obtain better quality of life after transplantation than MSD-HSCT in treatment of MDS-EB/AML-MRC.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adolescente , Adulto , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Qualidade de Vida , Estudos Retrospectivos , Irmãos , Adulto Jovem
20.
Zhonghua Xue Ye Xue Za Zhi ; 40(4): 306-311, 2019 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-31104442

RESUMO

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion: The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Hemoglobinúria Paroxística/terapia , Humanos , Estudos Retrospectivos , Irmãos , Resultado do Tratamento
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