RESUMO
A 20-year-old woman, with renal transplant complicated by recurrence of focal segmental glomerulosclerosis and post-transplant lymphoproliferative disorder, presented nearly 2 years after transplantation with fever, conjunctivitis, and sinus congestion. She was found to have severe adenovirus (ADV)-induced granulomatous interstitial nephritis, confirmed by immunohistochemical staining for ADV in the renal biopsy, without urinary symptoms, hematuria, or laboratory evidence of a change in allograft function. Fever, upper respiratory tract symptoms, and evidence of adenoviral infection in the allograft resolved with decreased immunosuppression and treatment with cidofovir and intravenous immunoglobulin. Creatinine rose during treatment and remained elevated, possibly related to cidofovir nephrotoxicity. Despite therapy and continued reduction in immunosuppression, asymptomatic low-level viremia persisted for a year. In renal transplant patients with ADV infection, allograft involvement should be highly suspected even without overt urinary symptoms or laboratory evidence of allograft dysfunction. Demonstration of allograft involvement may prompt alternative management that could limit continued allograft infection. No clear recommendations exist for management of asymptomatic ADV viremia in solid organ transplant patients.
Assuntos
Adenoviridae/classificação , Infecções por Adenovirus Humanos/virologia , Transplante de Rim/efeitos adversos , Nefrite Intersticial/virologia , Infecções Respiratórias/virologia , Adenoviridae/isolamento & purificação , Infecções por Adenovirus Humanos/tratamento farmacológico , Infecções por Adenovirus Humanos/patologia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Cidofovir , Citosina/administração & dosagem , Citosina/análogos & derivados , Citosina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Viremia , Adulto JovemRESUMO
Haplotype-tagging SNP analyses were conducted to identify molecular genetic substrates of quantitative phenotypes derived from performance on a Continuous Performance Task (CPT). Three hundred sixty-four individuals were sampled from 152 families ascertained on the basis of at least one child having ADHD. Probands, their affected and unaffected siblings, and parents were administered a CPT. Four different components of performance were analyzed and tested for association with SNPs from 10 candidate genes involved in monoaminergic function. After correcting for multiple comparisons and controlling for multiple individuals from the same family, significant associations were identified between commission errors and SNPs in the DRD2 gene (rs2075654, rs1079596), and between reaction time variability and a SNP in the NET gene (rs3785155). These findings suggest that commission errors and reaction time variability are excellent candidates as ADHD endophenotypes based on previously published criteria. Results also shed light on the molecular genetic basis of specific processes that may underlie the disorder.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Testes Neuropsicológicos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D2/genética , Alelos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Entrevistas como Assunto , Masculino , Núcleo Familiar , Pais , Fenótipo , IrmãosRESUMO
Intestinal Mycobacterium avium complex (MAC) infections are rare and can be challenging to diagnose. We describe a case of intestinal MAC infection in a kidney transplant recipient with 5 months of unexplained weight loss and abdominal pain who developed intestinal obstruction. Esophagoduodenoscopy with biopsies was performed but was nondiagnostic. Intestinal MAC was diagnosed via nasogastric aspirate culture results. The patient's symptoms rapidly improved after initiation of appropriate treatment, but he later died of aspiration pneumonia and candidemia.
Assuntos
Enteropatias/microbiologia , Transplante de Rim , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/microbiologia , Antibacterianos/uso terapêutico , Biópsia , Humanos , Enteropatias/diagnóstico , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológicoRESUMO
OBJECTIVE: Macroorchidism is one of the most well-described clinical characteristics of men with fragile X syndrome, but little information has been available regarding macroorchidism in prepubertal boys with fragile X. The purpose of this study was to learn whether macroorchidism is a characteristic of fragile X syndrome in prepubertal boys. METHODS: Clinical assessments were performed on 73 boys, 2.2 to 10.2 years, in whom fragile X either had been diagnosed or who had been referred for fragile X evaluations because of developmental delays. As part of these assessments, we measured testicular volumes using Prader orchiometer beads to find out if macroorchidism occurs before the onset of puberty. RESULTS: From 2.2 through 7 years, boys with fragile X have significantly larger mean testicular volumes than boys without fragile X, but macroorchidism (> or = 4.0 mL or > or = 2 times normal) only occurred in 1 of 27 boys with fragile X. From 8 to 10 years, all our patients with fragile X had clinically enlarged testicles (> or = 3.75 mL), and 7 of 9 boys with fragile X had macroorchidism (> or = 4.0 mL). The testicular volumes of control subjects were all < or = 3.0 mL. CONCLUSIONS: These findings suggest that macroorchidism occurs in some prepubertal boys with fragile X, but in this series it did not occur until age 6 and usually did not occur until after age 8.
Assuntos
Síndrome do Cromossomo X Frágil/patologia , Testículo/anatomia & histologia , Criança , Pré-Escolar , Síndrome do Cromossomo X Frágil/diagnóstico , Humanos , Masculino , Valores de Referência , Testículo/patologiaRESUMO
Mothers of 38 young girls with fragile X [fra (X)] between the ages of 4 and 11 years filled out the Child Behavior Checklist. Forty-seven percent of the girls had T scores greater than 70 on the hyperactive and social withdrawal scales. Between 26% and 15% of the girls also had high T scores on the depressed scale, on the schizoid-obsessive scale (for 6 to 11 year olds), on the schizoid or anxious scale (for 4 and 5 year olds), and on the aggressive scale. Although a high score on a scale of the Child Behavior Checklist does not constitute a medical diagnosis, it can alert clinicians to abnormal behaviors that warrant further assessment. These behaviors may also alert the clinician to the possibility of fra(X) syndrome when they are seen in their patients. The high percentage of girls with fra(X), who seem to have abnormal behaviors, provides good reason to diagnose them in their early years, not just for genetic counseling purposes, but so that they can receive appropriate intervention services.
Assuntos
Transtornos do Comportamento Infantil/genética , Síndrome do Cromossomo X Frágil/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Hipercinese/genética , Inteligência , Transtornos do Comportamento Social/genética , Inquéritos e QuestionáriosRESUMO
Mothers of 60 girls with fragile X [fra(X)] and 58 controls were asked to fill out the Conners' Parent's Questionnaire to determine if this commonly used checklist would detect behavior problems in young girls with fra(X). The mean T-scores were significantly different between the 2 groups of girls on 5 of the 6 factors on the Conners' Parent's Questionnaire and the girls with fra(X) had mean T-scores that were above the average range on both the Anxiety factor and the Hyperactivity Index factor. Significantly more girls had T-scores greater than 70 (> 98th centile) on 3 of the 6 factors. Twenty-three percent of the girls had T-scores greater than 70 on the Anxiety factor and 38% of the girls had T-scores greater than 70 on the Hyperactivity Index factor. This study suggests that some behavior problems will be reported frequently in young girls with fra(X) and should not be difficult for clinicians to detect.
Assuntos
Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/psicologia , Transtornos Mentais/etiologia , Transtornos Mentais/genética , Adolescente , Ansiedade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Pré-Escolar , Feminino , Humanos , Hipercinese/etiologia , Inteligência , Deficiências da Aprendizagem/etiologia , Mães , Testes Psicológicos , Transtorno da Personalidade Esquizotípica/etiologia , Inquéritos e QuestionáriosRESUMO
We report on 2 children with Townes-Brocks syndrome (TBS) and mental retardation. One child had mild hearing loss, but the other only had hearing loss at 8000 Hz. These cases suggest that there may be an increased incidence of mental retardation in individuals with TBS.
Assuntos
Deficiência Intelectual , Síndrome do Lobo Médio , Anormalidades Múltiplas , Criança , Feminino , Perda Auditiva , Humanos , MasculinoRESUMO
Fragile X syndrome is the leading form of hereditary mental retardation, but the condition is still underdiagnosed in young children. Because of concern that the fragile X phenotype is subtle in young boys and therefore contributes to underdiagnosis of the disorder, we evaluated 73 boys (36 with fragile X and 37 same-age boys who were fragile X negative) using a checklist that we devised to learn which characteristics might be the most useful for alerting professionals to this diagnosis. After a multiple comparisons adjustment, only 4 of 42 characteristics differed significantly in their distributions between the two groups of boys (P < 0.0012), but 10 other items may also have predictive value for fragile X syndrome (P < 0.01). Four additional items occurred in at least 80% of boys with fragile X and may also be helpful for the clinician. Professionals who work with developmentally delayed children should be aware of these 18 clinical characteristics and some of the behavior characteristics commonly seen in boys with fragile X so that they can readily diagnose patients.
Assuntos
Síndrome do Cromossomo X Frágil/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Masculino , Transtornos Mentais/fisiopatologia , FenótipoRESUMO
Fragile X syndrome normally arises as a consequence of large expansions (n >200) of a (CGG)(n) trinucleotide repeat in the promoter region of the FMR1 gene. The clinical phenotype is thought to result from hypermethylation of the repeat and adjacent upstream elements, with consequent down-regulation of transcription (transcriptional silencing). However, the relationship between repeat expansion and transcription has not been defined in the full mutation range. Using the method of quantitative (fluorescence) reverse transcriptase polymerase chain reaction, we demonstrated previously that FMR1 mRNA levels are substantially elevated in premutation (55 = n < 200) male carriers. In the current work, we report that in fragile X males with unmethylated alleles in the full mutation range (n > 200), FMR1 mRNA levels remain significantly elevated (mean 3.5-fold elevation; P = 6.7 x 10(-3)) relative to normal controls, even for alleles exceeding 300 repeats. This conclusion is independent of any assumption regarding the transcriptional activity of methylated alleles. However, if it were assumed that all methylated alleles were transcriptionally silent, the FMR1 mRNA levels for cells with unmethylated alleles would be even higher (mean 4.5-fold elevation; P = 2.1 x 10(-4)). These observations show that the full-mutation CGG expansion per se is not a strong impediment to transcription and that the apparent up-regulation of the FMR1 locus remains active in at least some cells with full-mutation alleles.
Assuntos
Metilação de DNA , Síndrome do Cromossomo X Frágil/genética , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA , Transcrição Gênica , Expansão das Repetições de Trinucleotídeos , Alelos , Proteína do X Frágil da Deficiência Intelectual , Heterozigoto , Humanos , Masculino , Mutação , Proteínas do Tecido Nervoso/biossíntese , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
We report on 4 individuals with the fragile X [fra(X)] syndrome and the Robin sequence (or elements of that sequence). To our knowledge, this association has been described in only one other boy. However, males with the fra(X) syndrome have been reported to have an increased incidence of cleft palate. We recommend that children with a cleft palate or the Robin sequence be assessed for developmental delays and a family history of mental retardation. The fra(X) syndrome may be one of the genetic causes of the Robin sequence and, when indicated, children with the sequence should be tested for fra(X).
Assuntos
Fissura Palatina/complicações , Síndrome do Cromossomo X Frágil/complicações , Deficiência Intelectual/complicações , Micrognatismo/complicações , Língua/anormalidades , Fissura Palatina/genética , Humanos , Recém-Nascido , Deficiência Intelectual/genética , Masculino , Micrognatismo/genéticaRESUMO
This paper reports the results of a longitudinal study of women at-risk to inherit the fragile X mutation. It addresses 1) how upsetting the women perceived their carrier information to be, 2) how serious a problem they perceive fragile X syndrome to be, and 3) descriptions of feelings about the carrier testing process. The study sample consisted of 42 women (20 carriers and 22 noncarriers). There were two measurement times (just prior to carrier testing and after learning actual carrier status). The measures used were a Fragile X Visual Analog Scale and a structured interview. At time 1, being at-risk was reported to be upsetting and fragile X syndrome was perceived to be a serious problem. For the women found to be carriers there was no change from time 1 to time 2 on any of the items. Significant change occurred in the non-carriers. They were significantly less upset at time 2 after receiving the results of their carrier test than at time 1. They also perceived fragile X syndrome to be a more serious problem than they did at time 1 and a more serious problem than the carriers at time 2. Themes found included concerns that carrier status for fragile X syndrome presented a barrier for having healthy biological children and concern for children's and grandchildren's adaptation to their own carrier status. Coping behaviors were activated to manage the emotions related to these concerns. The coping behaviors identified were minimization, acceptance of the possibility of being a carrier, a sense of being able to deal with the outcome of the carrier test, positive comparison, problem solving, and positive interpretation.
Assuntos
Síndrome do Cromossomo X Frágil/psicologia , Testes Genéticos/psicologia , Heterozigoto , Adaptação Psicológica , Adulto , Idoso , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Entrevista Psicológica , Estudos Longitudinais , Pessoa de Meia-Idade , Medição da DorRESUMO
This study surveyed obligate carriers of the fragile X syndrome fra(X) to ascertain opinions and attitudes regarding carrier testing. Female carriers of fra(X) syndrome were recruited during their visits to the Fragile X Clinic at Duke University Medical Center. Twenty-eight obligate carriers completed a 48 question structured interview and a visual analog scale (VAS). Strong trends in the responses were identified. Fra(X) syndrome was viewed as a very serious problem and the risk to offspring high. Subjects reported that prior knowledge of carrier status would have changed their reproductive plans. All felt that relatives should be informed about the inheritance of fra(X) syndrome; the mean age given for preferred age to inform their children of the inheritance of fra(X) syndrome was 12 years, and mean age given for optimal timing of carrier testing was 10 years. The women interviewed indicated that growing up with knowledge of their carrier status would have been preferable to learning this information as adults and they endorsed an aggressive approach to informing and testing their children. Further investigation is warranted to determine the psychological consequences of carrier testing for fra(X) syndrome in order to develop appropriate guidelines for testing and informing individuals at risk for fra(X) syndrome.
Assuntos
Síndrome do Cromossomo X Frágil/psicologia , Triagem de Portadores Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Criança , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Medição da DorRESUMO
The purpose of the study was to explore self-concept in women at risk for inheriting the fragile X mutation. Time 1 measures were obtained prior to carrier testing and Time 2 measures were collected approximately 5 months after learning carrier status. The sample consisted of 42 women from 17 families. Measures included the Tennessee Self-Concept Scale (TSCS), the fragile X Visual Analog Scale (VAS), and a structured interview. The TSCS provided a global measure of self-concept and the fragile X VAS and structured interview provided a contextual measure of self related to carrier status. Results indicated that there were no differences initially between carriers and noncarriers and no change from Time 1 to Time 2 on the TSCS. Analysis of the Time 1 fragile X VAS means for the total sample found a reduction in positive feelings about self. Analysis of the Time 2 fragile X VAS found that noncarriers reported improvement in feelings about self, with no change in feelings about self found in the carriers. Responses from the structured interview indicated that the feelings regarding self in the context of genetic testing are not related to global self-concept, but result from concerns regarding the implications of a positive carrier test for themselves and their families. This information highlights areas related to carrier testing that warrant further investigation and may ultimately result in modifications to the genetic counseling.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Triagem de Portadores Genéticos , Adulto , Feminino , HumanosRESUMO
A 2-year-old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27-q28 including deletion of FMR-1. Molecular analysis of the patient was recently described in Tarleton et al. [1993: Hum Mol Genet 2(11): 1973-1974] and the deletion was estimated to be at least 3 megabases (Mb). His mother had 2 FMR-1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a de novo event. The patient does not appear to have clinical or laboratory findings other than those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Deleção de Genes , Fragilidade Cromossômica , Humanos , Lactente , Cariotipagem , Masculino , FenótipoRESUMO
New molecular research has provided strong evidence for different forms of the fragile X mutation. These findings suggest the need to develop a more standardized and sensitive method for determining neurobehavioral effects of the fragile X gene(s), particularly for molecular studies of patients who do not have obvious mental retardation. This report describes a brief screening questionnaire designed to increase the detection of neurobehavioral dysfunction in individuals from fragile X families who are included in new molecular studies. Improved detection of the affected state in fragile X syndrome will allow more valid clinical data to be correlated with the important molecular information currently being collected.
Assuntos
Síndrome do Cromossomo X Frágil/psicologia , Comportamento , Cognição , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Neuropsicologia , Inquéritos e QuestionáriosRESUMO
Fragile X DNA studies were carried out on all obligate carriers of a large fragile X family with 10 mentally retarded individuals. One 64-year-old carrier man with an altered FMR-1 allele was not described as being mentally retarded or as having any limitations in function. He was married, raised 8 children, and worked as an auto mechanic. On examination, he had macrocephaly and mild macroorchidism but few of the other typical physical findings of males with fragile X syndrome. His Full Scale IQ is 73, and his Vineland Adaptive Behavior Composite is 73. On the Woodcock-Johnson Psycho-Educational Battery-Revised, he achieved standard scores of 64 in Reading, 55 in Math, and 83 in Knowledge. His DNA findings showed a broad smear on Southern blot analysis of 100-500 CGG repeats and no methylation at the EagI site upstream of the FMR-1 protein coding region. His FMR-1 protein production is 12% of normal. His daughters all have large premutations, with somatic instability in the size of the CGG repeat lengths. They all have evidence of academic underachievement and 2 have physical characteristics frequently described in individuals with fragile X.
Assuntos
Metilação de DNA , Síndrome do Cromossomo X Frágil/genética , Triagem de Portadores Genéticos , Repetições de Trinucleotídeos , Southern Blotting , DNA/sangue , Desoxirribonucleases de Sítio Específico do Tipo II , Feminino , Síndrome do Cromossomo X Frágil/fisiopatologia , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Mapeamento por RestriçãoRESUMO
Sixty-five parents of individuals affected by fragile X syndrome who attended the National Fragile X Conference in Portland, Oregon (1996), were asked to complete a survey assessing parental level of concern about carrier testing in children at risk for fragile X syndrome. All subjects completed a 15-item paper and pencil Likert response scale measure that was developed specifically for this study. The items included parental rights and duties, psychological adjustment, adaptation, discrimination, harm, childbearing, and interpersonal relationships. The major concern of the parents was that their children have knowledge of their carrier status prior to becoming sexually active and that their children be able to marry informed of their genetic risk. Mothers were significantly more concerned than fathers about raising their children with the knowledge of their carrier status. A sense of parental right to make the decision regarding carrier testing for children was associated with concerns about (1) behavioral or educational problems, (2) knowledge of carrier status prior to sexual activity or marriage, and (3) adjustment of the children to knowledge of their carrier status. As the sample was drawn from a unique population of parents, the results of this survey should be interpreted with caution. The findings of this study suggest a model of parents providing anticipatory guidance for their children to help them adjust to carrier information and for their children to have this knowledge prior to the possibility of reproduction.
Assuntos
Atitude Frente a Saúde , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/psicologia , Triagem de Portadores Genéticos , Pais/psicologia , Aconselhamento Genético/psicologia , Humanos , Risco , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
Five patients presenting with non-ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma free carnitine. L-carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Benzoatos/efeitos adversos , Carnitina/deficiência , Conservantes de Alimentos/efeitos adversos , Glicina/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Ácido Benzoico , Carnitina/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
This study examined the trajectories of cognitive development in boys under the age of 21 years with fragile X syndrome. By combining information from three centers, data from 66 boys were analyzed; only children who had been tested two or more times with the same psychometric instrument at one or more year intervals were included in this study. Results demonstrated that males with fragile X syndrome show a decline in IQ scores, with the most marked declines seen during the early pubertal period. All 22 children retested during the 11- to 15-year period showed IQ declines, suggesting a slowing of development associated with the onset of puberty. Before age 10 years, males with higher (as opposed to lower) pretest IQs were more likely to decline at subsequent testings. A single etiological factor may not be sufficient to account for the observed findings, as both changes in neurobiological- and task-related factors seem implicated in the slowing intellectual development of this population.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Inteligência , Aberrações dos Cromossomos Sexuais/genética , Adolescente , Criança , Pré-Escolar , Seguimentos , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Masculino , Teste de Stanford-Binet , Escalas de WechslerRESUMO
We conducted two multicenter studies on adaptive trajectories and profiles in males with fragile X syndrome. Study 1 longitudinally assessed 29 males ages 1-20 years using age-equivalent scores from the Vineland Adaptive Behavior Scales. Fragile X boys ages 1-10 years showed significant gains in adaptive skills from first to second testing; males ages 11-20 years were stable in their adaptive development. Study 2 cross-sectionally examined 132 males ages 1-20 years. Significant age-related gains were found in boys ages 1-10, particularly in preschool children. Subjects ages 11-20 showed increased variability and nonsignificant relations between age and adaptive skills. Preliminary findings from 26 young adults with fragile X syndrome ages 21-40 years showed stable age-equivalent adaptive scores during these years. Relative strengths in daily living skills and weaknesses in communication were only evident among older subjects. Significant relations were found between adaptive behavior standard scores and IQ; these two scores also showed age-related declines that likely parallel one another. Findings are related to adaptive features in other genetic syndromes, and to directions for future adaptive behavior research.