RESUMO
INTRODUCTION: Myeloablative conditioning before allogeneic HSCT during childhood exposes to serious long-term complications, especially gonadal dysfunction. Pubertal issues are less described than other post-HSCT sequelae in childhood. METHODS: Pubertal development and biological gonadal parameters were assessed in a retrospective monocentric cohort of prepubertal patients who underwent HSCT after myeloablative conditioning with TBI or busulfan between 1981 and 2017. RESULTS: Seventy-four patients (28 girls and 46 boys) were included. No spontaneous pubertal development was found in 50% of girls and 10% of boys (P < .001), and delayed puberty or no spontaneous pubertal development was found in 57% of girls and 24% of boys (P = .009). HRT was used in 82% of girls and 24% of boys (P < .001). In univariate analysis, TBI conditioning (P = .05), female sex (P < .001), acute GVHD (P = .05), extensive chronic GVHD (P = .021), steroid treatment >6 months (P = .016), and malignant diseases (P = .016) were associated with no spontaneous pubertal development, whereas TBI conditioning (P = .003) and extensive chronic GVHD (P = .005) were associated with delayed puberty. In multivariate analysis, factors independently associated with no spontaneous puberty onset were female sex (P = .001) and age >10 years (P = .033). Factors independently associated with delayed puberty were extensive chronic GVHD (P = .041) and age >10 years (P = .031). CONCLUSION: This study highlighted the toxicity of MAC in prepubescent children: TBI did worse, but this was especially true for the most susceptible patients (girls, leukemic patients, and patients older than 10 years). It suggests a possible role of GVHD in delayed puberty.
Assuntos
Bussulfano/efeitos adversos , Puberdade Tardia/etiologia , Puberdade/efeitos dos fármacos , Puberdade/efeitos da radiação , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adolescente , Criança , Pré-Escolar , Ciclofosfamida , Feminino , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
BACKGROUND: McCune-Albright syndrome is a rare disorder characterized by endocrine disorders, café-au-lait spots and fibrous dysplasia of bone that occurs early in life. METHODS: A series of 14 pediatric cases were followed between 1994 and 2013 by the competence center for rare endocrine diseases and constitutional bone diseases at CHU de Nancy (France). The diagnosis is based on the presence of at least two symptoms. RESULTS: The mean follow-up was 6 years (1-17 years). The sex ratio was six girls per boy. The incidence was 0.28 cases/million population/year. Mean age at diagnosis was 6 years. A mutation in the GNAS gene was found in 33% of patients tested. Gonadal involvement (13/14 cases), including early peripheral puberty and ovarian cysts in girls (82%) occurred on average at 4 years of age. Bone involvement (10/14 cases) appeared on average at 5 years of age and was most often multiple (80%) with fracture risk, and the skull, with a neurosensory risk. CONCLUSION: Clinical definition and methods of screening and monitoring can be improved to allow for an earlier intervention. It must be multidisciplinary and take into account the disability and quality of life of the patient.
Assuntos
Displasia Fibrosa Poliostótica/diagnóstico , Displasia Fibrosa Poliostótica/terapia , Doenças Ósseas , Manchas Café com Leite , Criança , Pré-Escolar , Feminino , Displasia Fibrosa Poliostótica/genética , França , Humanos , Comunicação Interdisciplinar , Masculino , Mutação , Ovário/fisiopatologia , Puberdade Precoce , Qualidade de Vida , Estudos Retrospectivos , Testículo/fisiopatologiaRESUMO
In a collaborative study, we investigated four 46,XX adolescent girls with Mayer-Rokitansky-Küster-Hauser syndrome and hyperandrogenism. Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T). Functional studies revealed partial repression of steroidogenic enzymes (normal repression of HSD3B2) contrasting with the abnormal reexpression of CYP17A1 enzyme in the OVCAR3 cell line. This fourth new WNT4 mutation confirms that this signaling molecule is involved in mullerian development and androgen biosynthesis repression in the ovary. Interestingly, this mutant partially lacks the capability to repress ovarian steroidogenic enzymes, with abnormal expression of 17α- hydroxylase.