Steroid 21-hydroxylase deficiency accounts for 95% of congenital adrenal hyperplasia (CAH) cases. Newborn screening has allowed for early detection of the disease, and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design Observational, retrospective, descriptive study based on the review of patient records who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 ( N = 58). Objective To describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency at the National Children's Hospital “Dr. Carlos Sáenz Herrera”, Caja Costarricense de Seguro Social (CCSS) in Costa Rica. Results 53% (31/58) of the patients were male and 80% (37/46) were born full term; 72% (42/58) had salt wasting phenotype, 9% (5/58) simple virilizing phenotype and 19% (11/58) non-classic phenotype. The most frequent variants were c.292+5G>A in 26% (15/58) of patients and Del/Del in 21% (12/58) of them. Conclusions The most frequent mutation in our study population was the c.292+5G>A, which was found in 15/58 patients. This rare variant has only been reported in three other studies so far but as an infrequent mutation in CAH patients. The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect.

Congenital hypothyroidism (CH) is one of the leading causes of intellectual impairment worldwide in infancy. The newborn screening has been able to prevent this mental disability, by a prompt initiation of therapy. Over the last years the incidence of HC has been increasing, mainly by lowering the screening cut-off level that leads to detection of milder cases. There is conflicting evidence if children with mild CH without treatment may develop neurological impairment in the future. Costa Rican newborn screening program in divided in three stages, measuring serum TSH concentrations from a heel prick aliquot of capillary blood dried onto a filter paper. Each test has different TSH cut-off values to determine if the newborn needs a clinical evaluation by an endocrinologist, needs another screening test or rules out hypothyroidism. We developed an observational, descriptive, retrospective study, based on medical records, to evaluate our newborn screening program performance. The study included the total national population of screened newborns from 2015 to 2017. Descriptive analysis and analytical analysis of variables were done, and test’s sensitivity and specificity were determined. The study analyzed 204.241 screened newborns, and 145 children referred to the Endocrinology Department of the National Children Hospital. This population represents 97% of births in these 3 years. The recall rate for a first positive test was 0.3%. Congenital hypothyroidism was confirmed in 73% of children referred to the Endocrinology Department because of a positive screening. Incidence was 1/1926 births. Detection rate was independent of birth weight nor gestational age. 45.3% of children diagnosed with CH were detected after the first screening test, 52.8% after the second screening test and 1.9% after the third screening test. Screening test analysis showed high sensitivity and specificity, with diagnostic accuracy above 90%, except for the third screening test. Free thyroxine measurements alone weren’t useful to predict CH diagnosis. The coverage of the national neonatal screening program extends almost to the entire population. Our test specificity is within international standards. Incidence of CH in Costa Rica is similar to that reported in medical literature. With current detection cut-off level, there is no need of performing a second mandatory evaluation to preterm and low weight newborns. The third screening test has a low performance rate, does not improve detection of children with CH significantly, and delays clinical evaluation by the endocrinologist. Prognosis of treated children with CH is excellent, with no evidence of severe cognitive deficit.

RESUMENLa enfermedad de Graves es un desorden autoinmune que constituye la principal causa de hipertiroidismo en niños; usualmente se manifiesta con bocio difuso, signos de oftalmopatía bilateral y la alteración bioquímica en las pruebas de función tiroidea. En ocasiones, los síntomas iniciales se presentan con manifestaciones psiquiátricas, lo que llega a ser un reto en el diagnóstico diferencial, ya sea del trastorno tiroideo primario o un trastorno psiquiátrico. Debido a la poca frecuencia con que esta manifestación de la enfermedad de graves se presenta en pediatría se expone aquí el caso de hipertiroidismo y psicosis aguda en un paciente pediátrico. PALABRAS CLAVEHipertiroidismo, Niños, Enfermedad de Graves, Psicosis aguda ABSTRACT Graves's disease is the most common cause of hyperthyroidism in children and adolescents. Generally presents itself as a diffuse goiter, clinical findings of bilateral ophthalmopathy and abnormal laboratory results in the thyroid function test. Sometimes, the psychiatric manifestations become the initial symptoms, what turns the differential diagnoses, from either the primary thyroid disorder or the psychiatric disease, in quite a challenge. Because of the low incidence of psychosis as manifestation of Graves' disease in children, we present a case of hyperthyroidism and acute psychosis in a child. KEYWORDSHyperthyroidism, children, Graves' disease, Psychosis. CASO CLINICOUn paciente masculino, costarricense, de 12 años de edad, fue admitido en el Hospital nacional de niños "Dr. Carlos Sáenz Herrera" por historia de alteración del comportamiento, bocio, proptosis, y alucinaciones visuales.El paciente es conocido sano, viviendo en albergue del PANI (Patronato Nacional de la Infancia, Costa Rica), con historia de alucinaciones que consistía en ver un "niño de 5 años de edad, pequeño, vestido de blanco, con espirales rojas en el pecho, el cual le decía que quemara el albergue donde se encontraba en ese momento, ya que no era un buen lugar". Las alucinaciones visuales del paciente durante esa semana se hicieron más frecuentes y además, comenzó a presentar un comportamiento agresivo, apático, ansioso, asociando irritación ocular, diaforesis, insomnio e inquietud por lo que los encargados del menor deciden consultar al hospital nacional psiquiátrico. Fue valorado

La diabetes mellitus neonatal es un raro desorden metabólico usualmente desarrollado en las primeras 6 semanas de vida, secundario a un grupo de mutaciones y defectos del desarrollo pancreático que puede desembocar en una catástrofe clínica si no se identifica tempranamente; se divide en una variante transitoria y una permanente, siendo la primera la más frecuente, con cerca de un 60% de los casos. El manejo inicial de ambas variantes es la insulinoterapia intensiva, que en la variante transitoria puede suspenderse usualmente en los primeros meses de vida. El síndrome de disregulación inmunológica, poliendocrinopatía y enteropatía ligada a X (IPEX por sus siglas en inglés), es una causa extremadamente rara de la variante permanente, casi siempre mortal, caracterizada por un inmunocompromiso severo, enteropatía, diabetes y dermatitis. En el estudio se describen 4 casos de diabetes mellitus neonatal diagnosticados en el Hospital Nacional de Niños de San José, Costa Rica: 2 correspondientes a una diabetes mellitus neonatal transitoria, 2 a una diabetes mellitus neonatal permanente y 1 de ellos correspondiente a un síndrome de IPEX.

: Congenital adrenal hyperplasia (CAH) is a group of enzymatic defects in cortisol biosynthesis. Steroid 21-hydroxylase deficiency accounts for greater than 90% of cases. Newborn screening has allowed for early detection of cases and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design: observational, retrospective, descriptive study based on review of patient files who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 (N=58). Objective: to describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency in Costa Rica. Results: 53.4% (31/58) of the patients were males and 80.4% (37/46) were born full term; 72.4% (42/58) had salt wasting phenotype, 8.6% (5/58) simple virilizing phenotype and 19.0% (11/58) non-classic phenotype. The most frequent genotypes were c.292+5G>A homo in 22.4% (13/58) of patients and Del/Del in 20.7% (12/58). Conclusions: The most frequent mutation in our study population was the c.292+5G>A, which was found in 13/58 patients. This rare variant has only been reported in other three studies so far but as an infrequent mutation in CAH patients (1,2,3). The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect. Reference : (1) Friaes et al ., Molecular Genetics and Metabolism. 2006;88:58-65. (2) Ezquieta et al ., Prenat Diagn. 2010;30:758-763. (3) Marino et al ., Clinical Endocrinology. 2011;75:427-435. Disclosure : All authors have nothing to disclose. Sources of Research Support : no financial support was used for this study, it was financed entirely by the authors. A donation for the statistical work was granted by the National Association for the Study of Diabetes, Endocrinology and Metabolism of Costa Rica (ANPEDEM). Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.