RESUMEN
BACKGROUND/AIM: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize NR0B1 deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes. RESULTS: In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the GK gene. A deletion extending to IL1RAPL1 was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed. CONCLUSIONS: Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect NR0B1 and contiguous gene deletions in patients with AHC. It is especially helpful for IL1RAPL1 deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy.
Asunto(s)
Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/fisiopatología , Receptor Nuclear Huérfano DAX-1/genética , Eliminación de Gen , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Sitios Genéticos , Adolescente , Hiperplasia Suprarrenal Congénita/metabolismo , Insuficiencia Suprarrenal , Adulto , Niño , Receptor Nuclear Huérfano DAX-1/metabolismo , Femenino , Estudios de Asociación Genética , Tamización de Portadores Genéticos/métodos , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Humanos , Insuficiencia Corticosuprarrenal Familiar , Lactante , Proteína Accesoria del Receptor de Interleucina-1/genética , Proteína Accesoria del Receptor de Interleucina-1/metabolismo , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/genética , Madres , Reacción en Cadena de la Polimerasa Multiplex , Técnicas de Amplificación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , SueciaRESUMEN
INTRODUCTION: McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly. CASE PRESENTATION: Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted. CONCLUSION: Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.
RESUMEN
BACKGROUND: Findings have been inconsistent regarding the effect of T1DM (type 1 diabetes) on age at menarche. OBJECTIVE: The purpose was to investigate in young German women with T1DM menarcheal age and factors potentially affecting menarche, including glycemic control, BMI (body mass index), relative T1DM duration (proportion of life with diabetes), insulin dose, and insulin therapy intensity. Initiated in 1990, the DPV program is an ongoing, prospective long-term longitudinal follow-up study to benchmark the quality of care provided to pediatric and, more recently, adult diabetes patients. Two hundered two German diabetes centers participated in nationwide data collection. Based on ethnicity and the availability of menarche and T1DM onset data as the main inclusion criteria, 643 young German women were selected from 11,629 female T1DM patients aged <20 years, recruited by referral, clinic or hospital ascertainment, or self report. Mean age at menarche (+/-SD) was 13.22 +/- 1.31 years, representing a delay of 0.52 years (p < 0.001) relative to the general population. Significant delay (p < 0.05) was also found for relative T1DM duration, BMI SD score, insulin dose, and HbA1c level, with a 1% increase in HbA1c resulting in a delay in menarche by 0.07 years. CONCLUSIONS: Age at menarche is delayed in type 1 diabetes mellitus. The delay increases with relative T1DM duration and poor quality of glycemic control.