Asunto(s)
Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Testosterona/análogos & derivados , Cromosoma X , Cromosoma Y , Adulto , Humanos , Hipogonadismo/sangre , Hipogonadismo/tratamiento farmacológico , Hipogonadismo/genética , Inyecciones Intramusculares , Masculino , Aberraciones Cromosómicas Sexuales/genética , Testosterona/administración & dosificación , Testosterona/uso terapéutico , Resultado del TratamientoRESUMEN
The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.
Asunto(s)
Mosaicismo , Aberraciones Cromosómicas Sexuales , Cromosoma Y , Adolescente , Adulto , Anciano , Preescolar , ADN/análisis , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Fenotipo , Estudios Retrospectivos , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/patología , Aberraciones Cromosómicas Sexuales/fisiopatología , Testosterona/uso terapéutico , Translocación GenéticaRESUMEN
A severely behaviourally disturbed three year old boy with the fragile-X syndrome was treated with intermittent folate therapy over a period of 2 years. No behavioural improvement was noted in this time but variations between cultural regimes for the successful detection of the fragile-X marker were observed.
Asunto(s)
Ácido Fólico/administración & dosificación , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Preescolar , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Humanos , Cariotipificación , Masculino , Linaje , Cromosoma X/efectos de los fármacosRESUMEN
Investigations of the effect of high dose folic acid treatment of fragile X syndrome in males has produced mixed results. However, no study had examined the possible drug effects of folic acid on non-fragile X control males. Therefore, we examined the effect of folic acid on fragile X males using non-fragile X control males. Subjects were assigned randomly to an ABA or BAB design. Duration of either folic acid or placebo condition was 4 months. Folic acid or placebo was given in a double-blind fashion. At the end of each condition, the subjects' behavior was assessed. At the end of the study, parents were asked to complete a questionnaire. Using parents' responses, we examined 22 items on the Autistic Descriptors Checklist and two subscales from the Vineland Adaptive Behavior Scale which corresponded to areas of behavior parents' noted to have shown improvement. We did not find significant differences between fragile X males and control males, within subjects, nor across folic acid and placebo conditions. Thus, our follow-up study confirms and extends our original findings, as well as those of other researchers: namely, that no dramatic changes in behavior result from high dose folic acid. Moreover, subtle improvements observed in earlier investigations were not confirmed.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Conducta/efectos de los fármacos , Niño , Preescolar , Ensayos Clínicos como Asunto , Síndrome del Cromosoma X Frágil/psicología , Humanos , Masculino , Distribución AleatoriaRESUMEN
Attentional deficits and hyperactivity frequently are major problems for fra(X) boys. This study evaluated the effectiveness of 2 stimulant medications, methylphenidate and dextroamphetamine compared to placebo in 15 children (13 males, 2 females) with the fra(X) syndrome. A double-blind crossover design was used with outcome measures which included parent and teacher behavior checklists, a controlled observation period, continuous performance tasks and an actometer measure of movement. When the children were treated with methylphenidate only, improvement was seen in socialization skills and attention span according to teacher checklists. Ten children were clinically considered responders and treatment was continued after the study was completed.
Asunto(s)
Dextroanfetamina/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Metilfenidato/uso terapéutico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/etiología , Niño , Preescolar , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/psicología , Humanos , MasculinoRESUMEN
Four boys with the combination of infantile autism and the fragile-X syndrome were given oral folic acid and placebo, according to a double-blind crossover design. One boy's behaviour appeared to improve on folic acid, but another boy did not seem to be affected at all. For the remaining two boys the results were equivocal. Further study of folic acid in the treatment of autistic boys with the fragile-X syndrome is warranted.
Asunto(s)
Trastorno Autístico/tratamiento farmacológico , Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Trastorno Autístico/complicaciones , Niño , Ensayos Clínicos como Asunto , Método Doble Ciego , Síndrome del Cromosoma X Frágil/complicaciones , Humanos , MasculinoRESUMEN
Three fragile X syndrome males were given 10 mg folic acid daily in a multiple-baseline, placebo study. Objective measures of memory skills, compliance, and behavioral appropriateness were taken during baseline, placebo, and treatment conditions. No change was evident in these variables during the drug trial. Thus, the findings shed doubt on the effectiveness of folic acid in increasing intellectual functioning or reducing behavior problems in individuals with fragile X syndrome. These results underscore the importance of operationally defined variables, double-blind observation and placebo treatment in elucidating the effects of folic acid.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Niño , Trastornos de la Conducta Infantil/tratamiento farmacológico , Preescolar , Ensayos Clínicos como Asunto , Método Doble Ciego , Humanos , Masculino , Memoria/efectos de los fármacosRESUMEN
We conducted an experimental trial of high-dose folic acid given to five males, ages 8 to 26 years, with the fra(X) syndrome. In this double blind study, each subject received 250 mg per day of folic acid for 3 months, followed by placebo for 3 months, and folic acid again for an additional three months. Based on IQ tests, behavior ratings, the Autistic Descriptors Checklist, and parental ratings, there was little evidence to suggest any positive effects seen during the administration of high-dose folic acid. Therefore, this study has provided little support for a hypothesis of benefit of high-dose folic acid in the treatment of the fra(X) syndrome.
Asunto(s)
Ácido Fólico/administración & dosificación , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Adulto , Conducta/efectos de los fármacos , Niño , Ensayos Clínicos como Asunto , Método Doble Ciego , Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/psicología , Humanos , Inteligencia/efectos de los fármacos , MasculinoRESUMEN
Ten males with the fragile X (fra(X] syndrome were treated with folic acid (10 mg/day) for 4 months in a double-blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effort to study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co-ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5-year-old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder. Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acid-free medium but not in cells cultured in a medium with added antifolate (methotrexate). This shows a "contamination effect" of folate-free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early-replicating X when culturing with folic acid-free medium. A synergistic suppression effect of "external folate" and BrdU is the most likely explanation of this phenomenon.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Adulto , Niño , Preescolar , Ensayos Clínicos como Asunto , Medios de Cultivo , Citogenética , Método Doble Ciego , Femenino , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Heterocigoto , Humanos , Inteligencia/efectos de los fármacos , Masculino , Persona de Mediana EdadRESUMEN
A double-blind, crossover study of a 10 mg folic acid per day (vs. placebo) treatment was carried out in 25 fra(X) males (ages 1-31 years). Each treatment period lasted 6 months. Before, during and after the study, the patients were assessed blindly with psychological, language and behavioral evaluations, and parent or caretaker reports were collected. Standardized testing did not show statistically significant changes in the group as a whole; psychological testing demonstrated a statistically significant improvement on folic acid in the prepubertal males. After uncoding, caretaker or parent reports also demonstrated behavioral improvements in the prepubertal males while being treated with folic acid.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Conducta/efectos de los fármacos , Niño , Preescolar , Ensayos Clínicos como Asunto , Método Doble Ciego , Ácido Fólico/administración & dosificación , Síndrome del Cromosoma X Frágil/psicología , Humanos , Lactante , Inteligencia/efectos de los fármacos , MasculinoRESUMEN
The effects of folic acid treatment were assessed in a 7-year-old boy with Fragile-X (fra(X] syndrome utilizing a within-subject experimental design. Dependent variables consisted of classroom behavior, activity level/impulsiveness, and attentiveness. While improvements in all dependent variables were observed during folic acid treatment in comparison to initial baseline/placebo conditions, these changes were maintained in a final return to the placebo condition. These results do not support unequivocally the effectiveness of folic acid treatment. Folic acid treatment may have facilitated behavior changes that were then maintained by natural contingencies in the child's environment.
Asunto(s)
Conducta/efectos de los fármacos , Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Atención/efectos de los fármacos , Niño , Síndrome del Cromosoma X Frágil/psicología , Humanos , Masculino , Actividad Motora/efectos de los fármacosRESUMEN
The effect of folic acid intake on the frequency of fragile X positive cells and some behavioural characteristics were evaluated in 5 boys and 4 adult males with the fragile X syndrome. The expression of fragile X was nullified in 6 and decreased in 3 of the 9 patients. Behavioural and motor ability were considered to have improved in 4 of the 5 boys but not in the 4 adults with fragile X syndrome.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Conducta/efectos de los fármacos , Niño , Preescolar , Fragilidad Cromosómica , Síndrome del Cromosoma X Frágil/psicología , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Monozygous twin 14-year-old mentally retarded boys with the fragile X syndrome were treated either with 10 mg folic acid by mouth daily or with a placebo for three test periods of 3-month duration each in a blind study. For each twin, tests of cognitive functioning, reading, spelling, and math skills, and linguistic and perceptual skills were compared. Although there was considerable variation in performance on these tests during the two baseline periods, there were no observable beneficial effects of therapy. The routine use of folic acid in patients with established mental retardation and the fragile X syndrome is not indicated.
Asunto(s)
Enfermedades en Gemelos , Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Gemelos Monocigóticos , Gemelos , Adolescente , Ensayos Clínicos como Asunto , Femenino , Ácido Fólico/sangre , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Humanos , Discapacidad Intelectual/tratamiento farmacológico , Discapacidad Intelectual/genética , Discapacidad Intelectual/psicología , Pruebas de Inteligencia , Aprendizaje , Masculino , Percepción , Embarazo , PsicometríaAsunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Discapacidad Intelectual/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Testículo/anomalías , Adulto , Citogenética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/psicología , Masculino , Pruebas Psicológicas , Vitamina B 12/uso terapéuticoRESUMEN
Forty-two patients with the fragile-X syndrome have been treated with oral folic acid, 0.5 mg/kg/d. An improvement of the behavior was observed in the majority of the cases, and evolution of the IQ showed a favorable tendency at the border of statistical significance. On the contrary, the addition to the treatment regime of methionine or of carnitine (carriers of methyl radicals) had unfavorable effects. In view of the few preliminary convergent observation recorded in literature, a continued trial of folic acid treatment seems justified. Simultaneously, however, research is indicated on monocarbon metabolism, probably affected in these patients.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Conducta/efectos de los fármacos , Niño , Evaluación de Medicamentos , Humanos , Pruebas de Inteligencia , Masculino , Factores de TiempoRESUMEN
Two brothers with fra(X) positive X-linked mental retardation (XLMR) were treated with folic acid. Initially a double blind cross-over design was employed followed by a long-term high dose trial. A decrease in the frequency of fra(X) positive cells was observed when low folic acid culture medium was used but not when an FUdR induction system was employed. Selected behavioral characteristics improved in both while receiving folic acid. Decreased hyperactivity, greater attention span, increased motor coordination, increased quantity and quality of speech were noted. Improvement in Leiter mental age and regression after cessation of treatment was seen in one subject but not in the other. Further controlled trials with larger numbers of subjects using high doses of folic acid over longer periods of time are needed to assess the possible benefits of this experimental form of treatment.
Asunto(s)
Ácido Fólico/uso terapéutico , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Adolescente , Niño , Fragilidad Cromosómica/efectos de los fármacos , Ácido Fólico/sangre , Síndrome del Cromosoma X Frágil/sangre , Síndrome del Cromosoma X Frágil/psicología , Humanos , Pruebas de Inteligencia , MasculinoRESUMEN
Hypothalamic-pituitary gonadotropin function was evaluated in two postpubertal XX males. Serum levels of LH and FSH were moderately elevated, and the serum testosterone level was low. A subnormal response by testicular Leydig cells to hCG was observed. The LH and FSH responses to LRH were normal. A significant LH increase was observed after castration. Weekly administration of testosterone enanthate (250 mg) for 10 consecutive weeks caused a reduction (greater than 75%) in gonadotropins and abolishment of the LRH pituitary response. No differences were observed in terms of gonadotropin dynamics compared with other forms of hypergonadotropic hypogonadism. These results indicate that XX males exhibit hypergonadotropic hypogonadism secondary to testicular failure with a preserved androgen responsiveness of the hypothalamic-pituitary unit.
Asunto(s)
Hormona Folículo Estimulante/sangre , Hipogonadismo/sangre , Hormona Luteinizante/sangre , Aberraciones Cromosómicas Sexuales/sangre , Adulto , Castración , Hormona Liberadora de Gonadotropina , Humanos , Hipogonadismo/etiología , Masculino , Persona de Mediana Edad , Aberraciones Cromosómicas Sexuales/complicaciones , Aberraciones Cromosómicas Sexuales/tratamiento farmacológico , Testículo/fisiología , Testosterona/análogos & derivados , Testosterona/uso terapéuticoRESUMEN
A decrease of frequency of a gap at the extremity of the long arm of the X chromosome (fragile site Xq27) is obtained by adjonction of monocarbons precursors to lymphocytes cultures. The efficacity of the treatments is precised by the analysis of 44 629 mitoses. For the first time, in one patient, parenteral administration of 5-formyl-tetrahydrofolate lead to a clinical improvement with concomitant disappearance of the gap.