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1.
Genet Med ; 24(6): 1274-1282, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35341653

RESUMO

PURPOSE: The purpose of this study was to delineate the effects of variable hormone replacement therapies on neuromotor function in a large cohort of males with 47,XXY from birth to adulthood. METHODS: A total of 270 participants aged 16 days to 17 years 11 months prenatally diagnosed with 47,XXY were assessed by their pediatric endocrinologist and were administered hormone replacement therapies accordingly. Infants and school-aged children with 47,XXY were administered neuromotor assessments during routine neurodevelopmental evaluations. For statistical analysis, participants were segregated on the basis of treatment status. Two-tailed t tests, 1-way analysis of variance, and post hoc analysis determined significant group differences on each assessment. RESULTS: In infants, the early hormonal treatment (EHT) group performed significantly better than the untreated group on fine motor and motor composite domains. In school-aged children, we observed significantly improved scores on fine motor control, coordination, agility, and strength domains among males treated with EHT (or any combination thereof) compared with those who did not receive early treatment. CONCLUSION: The highest treated combination group was associated with the highest neuromotor function, although the EHT group also often performed better than the other groups. This suggests EHT may be essential in promoting long-term optimal neuromotor outcome in males with an additional X.


Assuntos
Síndrome de Klinefelter , Adulto , Criança , Estudos de Coortes , Terapia de Reposição Hormonal , Humanos , Lactente , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/tratamento farmacológico , Síndrome de Klinefelter/genética , Masculino
2.
Am J Med Genet A ; 185(12): 3547-3553, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32618131

RESUMO

49,XXXXY is an X and Y chromosome variation that occurs in 1:85,000 to 1:100,000 live male births. Previous case studies have described boys with this disorder to be shorter than average when compared with boys with only one extra chromosome and with the mean stature in a small cohort reported to range from the seventh to 33rd percentile. The origin behind the possible differences in height between boys with 47,XXY and 49,XXXXY is currently unknown, however one study hypothesized that it was due to a difference in the expression of the SHOX gene. This study reports on the anthropometric measurements of 84 boys with 49,XXXXY. Forty-five percent of children with 49,XXXXY were found to be below the third percentile in height at the time of evaluation. In addition, 7.14% of the cohort were diagnosed and given treatment for growth hormone deficiency (GHD). The analysis of this cohort demonstrates that the below average heights seen throughout childhood in this population potentially begins prenatally and suggests that boys with 49,XXXXY may be at a higher risk for intrauterine growth restriction (IUGR) and GHD. Future research is needed to investigate the etiology of the poor growth in boys with 49,XXXXY and evaluate the incidence of GHD and IUGR in this population.


Assuntos
Nanismo Hipofisário/genética , Retardo do Crescimento Fetal/genética , Síndrome de Klinefelter/genética , Proteína de Homoeobox de Baixa Estatura/genética , Antropometria , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Nanismo Hipofisário/complicações , Nanismo Hipofisário/diagnóstico por imagem , Nanismo Hipofisário/fisiopatologia , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/fisiopatologia , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/genética , Humanos , Lactente , Recém-Nascido , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico por imagem , Síndrome de Klinefelter/fisiopatologia , Masculino , Aberrações dos Cromossomos Sexuais
4.
Am J Gastroenterol ; 105(3): 697-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20203647

RESUMO

The pathogenesis of celiac disease (CD)-associated short stature is still unclear. The authors showed that newly diagnosed CD patients have a high prevalence of positive antipituitary antibodies that correlates with height impairment. Given the association of CD with other autoimmune disease, these authors' findings show one possible etiology for the poor growth seen in children with CD.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Estatura , Doença Celíaca/imunologia , Hipófise/imunologia , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
6.
Appl Clin Genet ; 12: 191-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695472

RESUMO

47,XXY (Klinefelter syndrome [KS]) is the most common sex chromosomal aneuploidy (1:660), yet, despite this, only 25% of the males are ever diagnosed. Males with 47,XXY present with characteristic symptoms throughout their lifetime with typical physical and neurodevelopmental manifestations focused in growth, cognitive development, endocrine function, and reproduction. Studies have demonstrated that optimal outcomes are dependent on early detection combined with consistent and targeted neurodevelopmental treatment throughout the lifespan. During infancy and into the preschool years, individuals with 47,XXY commonly face deficits in growth and development in the areas of early hormonal, motor, speech, and behavioral development. As they transition into school, the primary neurodevelopmental concerns include language difficulty, executive dysfunction, behavior, and learning and reading deficits. Adults with 47,XXY often present with taller than average height, low levels of fertility, azoospermia, and elevated gonadotropin levels. These presentations may persist from early childhood through adulthood but can be mitigated by appropriate interventions. Early neurodevelopmental and hormonal treatment has been shown to have a minimizing effect on the physical and neurodevelopmental manifestations in individuals with 47,XXY. With innovative and current research studies, the features common to the neurodevelopmental profile of 47,XXY have been further expanded and defined. Further research is necessary to elucidate and understand the relationship between the brain, behavior, and the phenotypic profile of 47,XXY.

7.
Diabetes ; 55(5): 1443-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16644703

RESUMO

Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 +/- 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals.


Assuntos
Toxina da Cólera/farmacocinética , Diabetes Mellitus Tipo 1/fisiopatologia , Intestinos/fisiopatologia , Permeabilidade/efeitos dos fármacos , Doenças Autoimunes/genética , Doenças Autoimunes/fisiopatologia , Toxina da Cólera/genética , Claudina-1 , Claudinas , Diabetes Mellitus Tipo 1/genética , Família , Predisposição Genética para Doença , Haptoglobinas , Humanos , Intestinos/efeitos dos fármacos , Proteínas de Membrana/genética , Ocludina , Precursores de Proteínas
8.
J Pediatr Endocrinol Metab ; 29(2): 185-91, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26488602

RESUMO

BACKGROUND: Delayed discussion about infertility with individuals affected by Turner syndrome (TS) has been found to result in psychological and social harm. The aim of this study was to identify barriers experienced when discussing infertility and determine resource types that may facilitate this conversation. METHODS: An electronic survey, given to caregivers of girls with TS diagnosed at <5 years. RESULTS AND CONCLUSIONS: Fifty percent of parents surveyed had spoken to their daughter about their possible infertility. Parents who had not yet discussed infertility with their daughter had younger daughters and reported more barriers in having the conversation. Although most individuals did not use resources to facilitate the conversation, they did express interest in additional resources.


Assuntos
Barreiras de Comunicação , Infertilidade Feminina/fisiopatologia , Síndrome de Turner/fisiopatologia , Feminino , Humanos
9.
Case Rep Pediatr ; 2015: 738571, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26101681

RESUMO

We describe an alternative strategy for management of severe growth failure in a 14-year-old child who presented with advanced chronic kidney disease close to puberty. The patient was initially treated with growth hormone for a year until kidney transplantation, followed immediately by a year-long course of an aromatase inhibitor, anastrozole, to prevent epiphyseal fusion and prolong the period of linear growth. Outcome was excellent, with successful transplant and anticipated complete correction of height deficit. This strategy may be appropriate for children with chronic kidney disease and short stature who are in puberty.

10.
Horm Res Paediatr ; 84(2): 79-87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25966824

RESUMO

BACKGROUND/AIMS: Growth hormone (GH) treatment regimens for children with non-GH-deficient, idiopathic short stature (ISS) have not been optimized. To compare the efficacy, efficiency, and safety of an individualized, target-driven GH regimen with standard weight-based dosing after 4 years of treatment. METHODS: This is a 4-year, open-label, multicenter, randomized trial comparing individualized, formula-based dosing of Genotropin® versus a widely used ISS dose of Genotropin®. Subjects were prepubertal, had a bone age of 3-10 years for males and 3-9 years for females, were naive to GH treatment, and had a height standard deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the individualized-dosing group was further randomized to either 0.18 or 0.24 mg/kg/week. RESULTS: At 4 years, subjects in all treatment regimens achieved similar average height gains of +1.3 SDS; however, the individualized dosing regimen utilized less GH to achieve an equivalent height gain. CONCLUSION: Individualized, formula-based GH dosing, followed by a dose reduction after 2 years, provides a more cost-effective growth improvement in patients with ISS than currently employed weight-based regimens.


Assuntos
Estatura/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Desenvolvimento Ósseo/efeitos dos fármacos , Criança , Pré-Escolar , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Feminino , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Masculino , Pais , Medicina de Precisão , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
12.
Proc Natl Acad Sci U S A ; 103(46): 17414-9, 2006 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-17088564

RESUMO

Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Canal de Potássio Kv1.3/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Eletrofisiologia , Feminino , Humanos , Canal de Potássio Kv1.3/antagonistas & inibidores , Proteínas Associadas a Pancreatite , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Receptores CCR7 , Receptores de Quimiocinas/metabolismo , Linfócitos T/patologia
13.
J Pediatr ; 145(4): 549-51, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15480383

RESUMO

Growth failure is common in children with untreated HIV, although growth hormone (GH) deficiency is rare. Treatment with highly active antiretroviral therapy usually results in resumption of normal growth. We report the cases of 2 children with growth failure despite stable full suppression of viremia who were found to be GH deficient.


Assuntos
Terapia Antirretroviral de Alta Atividade , Transtornos do Crescimento/etiologia , Infecções por HIV/complicações , Hormônio do Crescimento Humano/deficiência , Criança , Pré-Escolar , Transtornos do Crescimento/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Proteínas Recombinantes/uso terapêutico
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