25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis.

The role of Vitamin D in the development of type 1 diabetes (T1D) is controversial. The Canary Islands have the highest incidence of childhood-onset T1D in Spain and one of the highest in Europe. We aimed to evaluate 25OHVitamin D concentrations in a Canarian pediatric population, to assess the existence of seasonal variation, to study their association with T1D, and to evaluate the role of acidosis in its levels. In a retrospective, case-control study, we obtained data from 146 T1D patients (<15 years of age) and 346 control children; 25OHVitamin D concentrations were assessed in serum by automatic ChemiLuminescence ImmunoAssay technology. We found significantly higher 25OHVitamin D levels in the summer and autumn months and an inverse correlation between T1D and age; 25OHVitamin D sufficiency was similar in both groups (44.5% vs. 45.1%), with significant differences in the percentage of patients presenting vitamin D deficiency (11.6% (T1D) vs. 16.4% (controls)). When stratified according to the presence of ketoacidosis at sampling, only patients with acidosis showed lower 25OHVitamin D concentrations than controls. Despite its subtropical geographic location, Vitamin D deficiency is frequent in children in Gran Canaria, and 25OHVitamin D concentrations show seasonal variation. After adjusting for acidosis, no differences were found between children with and without T1D.

Hiperinsulinismo congénito en Gran Canaria / Congenital hyperinsulinism in Gran Canaria, Canary Isles

Introducción: El hiperinsulinismo congénito (HC) es una patología seria caracterizada por la aparición de hipoglucemias graves. Las mutaciones patogénicas en los genes ABCC8 y KCNJ11 son la causa más frecuente, aunque también se han descrito en otros (GCK, GLUD1, HADH, HNF1A, HNF4A, SLC16A1, UCP2, HK1) y asociado a diferentes síndromes. Material y métodos: Revisión retrospectiva de los pacientes con diagnóstico de HC en nuestra unidad durante los últimos 18años (2001-2018). El análisis genético incluyó un cribado de 11genes en ADN genómico a partir de sangre periférica (ABCC8, GCK, GLUD1, HADH, HNF1A, HNF4A, INSR, KCNJ11, SLC16A1, UCP2, SLC25A15). Objetivos: Realizar una caracterización clínica y genética de los casos diagnosticados de HC en nuestro medio. Resultados: Desde 2001 hemos tenido 10casos de HC persistente. Siete presentaron mutaciones en el gen ABCC8, uno en el gen HNF4α y en dos pacientes no se encontraron mutaciones patogénicas en los genes analizados. Cuatro pacientes presentaron mutaciones no descritas previamente. Se recurrió a la pancreatectomía en dos de los casos. El valor mínimo de insulina detectado en hipoglucemia fue de 6,81μUI/ml. La incidencia de HC persistente para Gran Canaria y Lanzarote es de 1/15.614. Conclusiones: Cuatro pacientes presentaron mutaciones no descritas. El gen más frecuentemente afectado fue ABCC8. El 20% de los pacientes requirieron pancreatectomía. En todos los pacientes se objetivó un valor de insulina ≥6,81μUI/ml en el momento del diagnóstico. La incidencia de HC en Gran Canaria es elevada. (AU)

Introduction: Congenital hyperinsulinism (CH) is a severe disorder characterised by the appearance of severe hypoglycaemia. Pathogenic mutations in the ABCC8 and KCNJ11 genes are the most frequent cause, although its appearance also been associated to mutations in other genes (GCK, GLUD1, HADH, HNF1A, HNF4A, SLC16A1, UCP2, HK1), and with different syndromes. Materials and methods: Retrospective review of patients diagnosed with CH in this unit during the last 18years (2001-2018). Genetic analysis included screening for 11genes in genomic DNA from peripheral blood (ABCC8, GCK, GLUD1, HADH, HNF1A, HNF4A, INSR, KCNJ11, SLC16A1, UCP2, and SLC25A15). Objective: To carry out a clinical and genetic characterisation of the diagnosed cases of CH in Gran Canaria. Results: There have been 10cases of persistent CH since 2001. Seven of them had mutations in the ABCC8 gene, one in the HNF4α gene, and in two patients, no pathogenic mutations were found in the analysed genes. Four patients presented with previously undescribed mutations. Pancreatectomy was performed in two of the cases. The minimum insulin value detected in hypoglycaemia was 6.81μIU/ml. The incidence of persistent CH for Gran Canaria and Lanzarote is 1/15,614. Conclusions: Four patients had previously undescribed mutations. The most frequently affected gene was ABCC8. Pancreatectomy was required in 20% of the patients. An insulin value of ≥6.81μIU/ml was observed in all patients at the time of diagnosis. The incidence of CH in Gran Canaria is high. (AU)

Congenital hyperinsulinism in Gran Canaria, Canary Isles.

INTRODUCTION: Congenital hyperinsulinism (CH) is a severe disorder characterised by the appearance of severe hypoglycaemia. Pathogenic mutations in the ABCC8 and KCNJ11 genes are the most frequent cause, although its appearance also been associated to mutations in other genes (GCK, GLUD1, HADH, HNF1A, HNF4A, SLC16A1, UCP2, HK1), and with different syndromes. MATERIALS AND METHODS: Retrospective review of patients diagnosed with CH in this unit during the last 18 years (2001-2018). Genetic analysis included screening for 11 genes in genomic DNA from peripheral blood (ABCC8, GCK, GLUD1, HADH, HNF1A, HNF4A, INSR, KCNJ11, SLC16A1, UCP2, and SLC25A15). OBJECTIVE: To carry out a clinical and genetic characterisation of the diagnosed cases of CH in Gran Canaria. RESULTS: There have been 10 cases of persistent HC since 2001. Seven of them had mutations in the ABCC8 gene, one in the HNF4α gene, and in two patients, no pathogenic mutations were found in the analysed genes. Four patients presented with previously undescribed mutations. Pancreatectomy was performed in two of the cases. The minimum insulin value detected in hypoglycaemia was 6.81 µIU/mL. The incidence of persistent CH for Gran Canaria and Lanzarote is 1/15,614. CONCLUSIONS: Four patients had previously undescribed mutations. The most frequently affected gene was ABCC8. Pancreatectomy was required in 20% of the patients. An insulin value of ≥6.81 µIU/mL was observed in all patients at the time of diagnosis. The incidence of CH in Gran Canaria is high.

Síndrome de Noonan: actualización genética, clínica y de opciones terapéuticas / Noonan syndrome: genetic and clinical update and treatment options

El síndrome de Noonan (SN) es una enfermedad de origen genético relativamente frecuente cuyas manifestaciones fundamentales son la talla baja, la cardiopatía congénita y un fenotipo facial característico. La causa del síndrome de Noonan y de otras enfermedades clínicamente solapadas como el síndrome de Noonan con lentiginosis múltiple (anteriormente llamado síndrome LEOPARD), el cardiofaciocutáneo o el síndrome de Costello, son mutaciones en genes que codifican para proteínas de la vía de señalización de las RAS-MAPKinasas. Debido a este sustrato común este grupo de enfermedades son denominadas colectivamente «rasopatías». A pesar de los avances genéticos de las últimas décadas, cerca de 20% de pacientes no tienen causa genética identificada, y el diagnóstico sigue siendo clínico. El síndrome de Noonan se caracteriza por una alta heterogeneidad clínica y genética, con afectación variable, y cambiante con la edad, de múltiples órganos y sistemas. Debido a esta variabilidad es fundamental que los médicos involucrados en su cuidado estén familiarizados con sus manifestaciones y conozcan las recomendaciones de seguimiento, incluido el seguimiento del crecimiento y desarrollo. Hasta la fecha los escasos datos de crecimiento con GH a talla adulta dan resultados de ganancia de talla moderados, semejantes a los obtenidos en el síndrome de Turner. La hiperactivación de la vía RAS-MAPK como base común de esta familia de enfermedades brinda una oportunidad única para el desarrollo de tratamientos dirigidos a la etiología de estos trastornos

Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches

[Noonan syndrome: genetic and clinical update and treatment options]. / Síndrome de Noonan: actualización genética, clínica y de opciones terapéuticas.

Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies¼. Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches.

Carbohydrate metabolism changes in cystic fibrosis.

AIMS: To assess the prevalence of impaired glucose tolerance (ITG) and diabetes mellitus (DMRCF) in a group of patients with cystic fibrosis (CF). To study clinical status-related variables and to compare age with the evolution of their carbohydrate metabolism (CHM). PATIENTS AND METHODS: Thirty patients with CF (1.5-26 years). Oral glucose tolerance test (OGTT) in 28 patients. RESULTS: Three patients (10%) showed ITG and four DMRCF (13.3%). CF patients with impaired CHM (ICHM) were older (p = 0.006), and had longer times since diagnosis and first sputum colonization (p = 0.001, p < 0.001). Homozygous deltaF508 mutation was significant (p = 0.001). Insulin peak, area under the curve for insulin, insulin resistance, insulin sensitivity, and pancreatic beta-cell function were all significant. CONCLUSIONS: ICHM was present in 23.3%. Age, time since diagnosis of CF, first sputum colonization and homozygous deltaF508 mutation were significantly associated. CHM in patients with CF is similar to that in the population without CF in the early years.