ABSTRACT
El SD22q11.2 está asociado a síndromes de DiGeorge, velocardiofacial, facioconotruncal y Cayler, reconocidos con la misma etiología: microdeleción 22q11.2. El fenotipo es variable y presenta cardiopatía conotruncal (CC), dismorfias faciales, anomalías palatinas, inmunodeficiencias y trastornos del neurodesarrollo. Las manifestaciones endocrinológicas que predominan son talla baja, hipocalcemia neonatal asociada a hipoparatiroidismo y disfunción tiroidea. El 90% de los afectados presenta una deleción típica de 3-Mb, mientras que el resto tiene deleciones de menor tamaño o deleción localizada más distal a la región crítica . El objetivo del trabajo es identificar en una cohorte de 63 pacientes con sospecha clínica de SD22q11.2, la presencia de la microdeleción 22q11.2 empleando como método diagnóstico la técnica de FISH y describir brevemente las características clínicas más prevalentes que presentan los pacientes con resultado de FISH positivo y negativo. La microdeleción 22q11.2 se identificó en el 38% (24/63) de los pacientes estudiados. Las características clínicas más prevalentes en este grupo fueron las cardiopatías congénitas conotruncales (95,6%), microcefalia (50%), inmunodeficiencias (50%), hipocalcemia (48,8%), anomalías del paladar (45,8%), retraso del desarrollo y déficit cognitivo (41,5%). En nuestro hospital, el algoritmo diagnóstico para la detección de la microdeleción 22q11.2 es el cariotipo de alta resolución y el estudio por la técnica de FISH.
DS22q11.2 is associated with a wide spectrum of clinical disorders (DiGeorge, velocardiofacial, facioconotrunal and Cayler syndromes) known to arise from the same etiology 22q11.2 microdeletion The phenotype is variable and includes conotruncal cardiac defect (CCD), facial phenotype, palate anomalies, inmunodeficiency and developmental disorders. The endocrine manifestations are short stature (ST), neonatal hypocalcemia due to hypoparathyroidism, and thyroid dysfunction. In 90% of patients with 22q11.1 deletion a common 3-Mb deletion has been found, whereas the rest of cases share a smaller deletion or more distal atypical deletions. The aim of the present study was to identify the 22q11.2 microdeletion by FISH in 63 patients from the Genetic and Endocrinology Division between 2002 and 2017 who had more than one clinical feature of DS22q11. 2. High resolution karyotype and fluorescent in situ hybridization (FISH) were performed with different commercial probes. The 22q11.2 microdeletion was demonstrated in 24/63 patients (38%). The more relevant clinical features in this group were: conotruncal cardiac defect (95.6%), microcephaly (50%), immunodeficiency (50%), hypocalcaemia (48.8%) palate anomalies (45.8%), development delay and cognitive deficit (41.5%). In our hospital, the diagnostic algorithm for the detection of the 22q11.2 microdeletion is the high resolution karyotype and the study by the FISH technique.
Subject(s)
Humans , In Situ Hybridization, Fluorescence , DiGeorge Syndrome , 22q11 Deletion Syndrome , Endocrinology , GeneticsABSTRACT
El síndrome de poliquistosis ovárica (SOP) es un cuadro que acompaña a la mujer durante toda su vida y se caracteriza por hiperandrogenismo y anovulación crónica. Se presenta comúnmente en la adolescencia y es eldesorden endócrino más frecuente en mujeres en edad reproductiva en el mundo. A largo plazo se asocia con morbilidad significativa que incluye alteraciones en la salud reproductiva, disfunción psicosocial, síndrome metabólico, enfermedad cardiovascular e incremento en el riesgo de cáncer. Su etiología es desconocida aún, sin embargo, a lo largo de las tres últimas décadas, diferentes grupos de expertos en el mundo han elaborado guías para el diagnóstico y manejo de esta enfermedad. Existen tres grupos diferentes de criterios en el mundo pero están basados principalmente en información y experiencia en el manejo de mujeres adultas. Estos criterios diagnósticos no son completamente trasladables a las adolescentes. El objetivo de este artículo es acercar al pediatra clínico los elementos para alcanzar un entendimiento práctico y simplificar el manejo inicial del diagnóstico del cuadro de SOP en la adolescencia, concientizar acerca de las comorbilidades asociadas y su posibilidad de prevención para evitar riesgos en la vida adulta.
The polycystic ovarian syndrome (PCOS) is a lifelong disorder characterized by hyperandrogenism and chronicanovulation. It becomes manifest soon after puberty and it is the most frequent endocrine disorder in women at reproductive age in the world. In the long term it is associated with significant morbidity that includes alterations in reproductive health, psychosocial dysfunction, metabolic syndrome, cardiovascular disease and increased risk of cancer. Its etiology is still unknown, however, over the last three decades; several guidelines for the diagnosis and management of this disease have been developed. Three different sets of diagnostic criteria have been established to define this disease in adult women, but these diagnostic criteria are not completely transferable to adolescents. The objective of this article is to give pediatricians the elements for a practical understanding to simplify the initial management of the diagnosis of PCOS in adolescence and to raise awareness on the likelihood of associated comorbidities and that appropriate intervention could prevent later complications in adult life
Subject(s)
Female , Polycystic Ovary Syndrome , Hyperandrogenism , HirsutismABSTRACT
El crecimiento y la maduración física del niño y del adolescente transcurre por diversas etapas observándose cambios en la talla y velocidad de crecimiento característicos que son consecuencia entre otros factores, de cambios hormonales en el sistema o eje de la hormona de crecimiento (GH). Los principales componentes de este eje con utilidad clínica en la etapa infanto-juvenil son la GH, el factor de crecimiento insulino símil tipo I (IGF-I) y las proteínas de transporte. La GH es secretada por la hipófisis en forma de pulsos a la circulación y esto es uno de los principales factores que condicionan su utilidad como marcador de deficiencia de GH. La medición de GH en condiciones basales únicamente tiene valor diagnóstico cuando se obtiene en hipoglucemia y especialmente si se trata de un neonato. Es necesario entonces, en el resto de los casos, evaluar la capacidad de secreción de GH mediante pruebas funcionales de estímulo estandarizadas. Los factores dependientes de GH son considerados biomarcadores fidedignos de la acción de GH. Sin embargo, su concentración varía ampliamente durante la etapa pediátrica obligando su interpretación en el contexto de valores de referencia establecidos según la edad, sexo y desarrollo puberal. El presente trabajo revela los profundos cambios fisiológicos en los componentes del sistema de la GH que ocurren en la etapa pediátrica y los recaudos que deben tenerse en cuenta cuando se utilizan en el diagnóstico de la deficiencia de GH
Among other factors, the postnatal growth and physical maturation of children and adolescents (characterized by changes in the size and growth velocity rates) are influenced by components of the growth hormone (GH) system. GH, the type I insulin-like growth factor (IGF-I) and their transport proteins constitute the more relevant biochemical tools for the GH deficiency (GHD) diagnosis in pediatrics. The GH is secreted by the pituitary gland into the circulation in pulses and this pulsatility limits its usefulness, with the exception of a random basal GH in neonates under hypoglycaemia. Therefore, it is necessary to evaluate GH secretion status in standardized functional tests. IGF-I and IGFBP-3 are considered reliable biomarkers of GH action. However, these GH-dependant biomarkers widely vary in the paediatric period, forcing their interpretation in the context of confident reference values according to age, sex and pubertal development. The present revision reveals the profound physiological changes in the components of the GH system throughout the whole pediatric period and the situations that must be taken into account when they are used in the diagnosis of GHD
Subject(s)
Humans , Growth Hormone , Growth , Pediatrics , Growth and Development , EndocrinologyABSTRACT
Isolated growth hormone deficiency (IGHD) may result from deletions/mutations in either GH1 or GHRHR genes. The objective of this study was to characterize the molecular defect in a girl presenting IGHD. The patient was born at 41 weeks of gestation from non-consanguineous parents. Clinical and biochemical evaluation included anthropometric measurements, evaluation of pituitary function, IGF-I and IGFBP-3 levels. Molecular characterization was performed by PCR amplification of GH1 gene and SmaI digestion of two homologous fragments flanking the gene, using genomic DNA from the patient and her parents as templates. At 1.8 years of age the patient presented severe growth retardation (height 61.2 cm, -7.4 SDS), truncal obesity, frontal bossing, doll face, and acromicria. MRI showed pituitary hypoplasia. Laboratory findings confirmed IGHD. GH1 gene could not be amplified in samples from the patient while her parents yielded one fragment of the expected size. SmaI digestion was consistent with the patient being compound heterozygous for 6.7 and 7.6 Kb deletions, while her parents appear to be heterozygous carriers for either the 6.7 or the 7.6 Kb deletions. We have characterized type IA IGHD caused by two different GH1 gene deletions, suggesting that this condition should be considered in severe IGHD, even in non-consanguineous families. Arq Bras Endocrinol Metab. 2012;56(8):558-63.
A deficiência isolada do hormônio do crescimento (DIGH) pode ser resultado de deleções/mutações no gene GH1 ou no gene GHRHR. O objetivo deste estudo foi caracterizar o defeito molecular em uma menina que apresenta DIGH. A paciente nasceu às 41 semanas de gestação de pais não consanguíneos. As avaliações clínica e bioquímica incluíram medidas antropométricas, avaliação da função pituitária e concentrações de IGF-I e IGFBP-3. A caracterização molecular foi feita por meio de amplificação do GH1 por PCR e digestão com SmaI de dois fragmentos homólogos flanqueando o gene, usando-se DNA genômico da paciente e de seus pais como padrões. Com 1,8 ano de idade, a paciente apresentou atraso grave no crescimento (altura 61,2 cm, -7.4 DP), obesidade central, protuberância frontal, face de boneca e acromicria. A RM mostrou hipoplasia pituitária. Os achados laboratoriais confirmaram a DIGH. O gene GH1 não pôde ser amplificado nas amostras da paciente, enquanto as amostras de seus pais produziram um fragmento do tamanho esperado. A digestão com SmaI foi consistente com a paciente ser heterozigota composta para deleções para 6,7 e 7,6 Kb, enquanto seus pais parecem ser carreadores heterozigotos para deleções de 6,7 ou 7,6 Kb. Caracterizamos a DIGH tipo IA causada por duas deleções diferentes no gene GH1, sugerindo que essa condição pode ser considerada na DIGH grave, mesmo em famílias não consanguíneas. Arq Bras Endocrinol Metab. 2012;56(8):558-63.
Subject(s)
Female , Humans , Infant, Newborn , Dwarfism, Pituitary/genetics , Human Growth Hormone/genetics , Locus Control Region/genetics , Sequence Deletion/genetics , Base Sequence , Heterozygote , Phenotype , Polymerase Chain Reaction , Severity of Illness IndexABSTRACT
La hormona de crecimiento humana (hGH) circula parcialmente unida a su proteína de transporte de alta afinidad (GHBP) la cual resulta del clivaje proteolítico del dominio extracelular del receptor de GH. Recientemente la enzima TACE se identificó como la metaloproteasa responsable del clivaje y liberación de GHBP a circulación. Aunque aún se desconoce la función específica de esta proteína de transporte, distintos trabajos en la literatura demuestran efectos que potencian y efectos inhibitorios sobre la acción de GH. Por otro lado, existen evidencias que demuestran una fuerte relación entre la GHBP y el nivel de receptor de GH en el hígado en situaciones fisiológicas y patológicas. Esto permitió proponer a la determinación de GHBP en suero como un marcador periférico de la abundancia del receptor de GH en los tejidos. La determinación de la concentración de GHBP sería de especial interés para evaluar pacientes con diagnóstico probable de insensibilidad a la acción de GH y orientar el posterior estudio de anormalidades en el gen del receptor de GH. En la presente revisión, también se abordan dificultades metodológicas relacionadas a la medición de GHBP sérica.
Human circulating growth hormone (GH) is partly bound to a high-affinity binding protein (GHBP) which is derived from proteolytical cleavage of the extracellular domain of the GH receptor. Recently, the metalloproteinase TACE has been identified as an important enzyme responsive for inducing GHBP shedding. Although the specific function of GHBP is not fully known, both enhancing and inhibitory roles of this binding protein on GH action have been proposed. Many reports have demonstrated a close relationship between GHBP and the liver GH receptor status in physiological conditions and diseases. Moreover, serum GHBP measurement has been proposed as an useful peripheral index of the GH receptor abundance. Related to the latter, circulating GHBP concentration would be of special interest for the evaluation of GH insensitivity due to GH receptor gene abnormalities. In addition, the present review also focus on methodological problems concerning serum GHBP measurement.