Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of normal pubertal development due to deficient gonadotropin-releasing hormone (GnRH) secretion or action, and is caused by genetic defects in several genes. Mutations in the CHD7 gene cause CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear abnormalities), but have also been found in patients with isolated CHH. The aim of this study was to identify CHD7 mutations in patients with CHH. Fifty Portuguese patients with CHH were screened for mutations in the CHD7 gene by DNA sequencing. Eight (16%) patients had CHD7 rare sequence variants that consisted of six missense (p.Gly388Glu, p.His903Pro, p.Thr1082Ile, p.Val1452Leu, p.Asp1854Gly, and p.Arg2065His) and two synonymous (p.Ser559Ser, and p.Ala2785Ala) mutations. Five of these mutations have never been reported before. Three CHD7 mutations occurred in patients that had mutations in additional CHH-genes. This study uncovered novel genetic variants that expand the known spectrum of mutations associated with CHH. The frequency of CHD7 mutations in this cohort was higher than that of other major CHH-genes and confirms the importance of including CHD7 in the genetic testing of CHH, even in the absence of additional CHARGE features.

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Background/objective: Mauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS. Materials and methods:A retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed. Results: From a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13---17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia. Conclusions: Although MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control. © 2012 SEEN. Published by Elsevier España, S.L. All rights reserved. PALABRAS CLAVESíndrome de Mauriac; Diabetes mellitus; Adolescencia El síndrome de Mauriac todavía existeResumen Introducción/objetivo: El síndrome de Mauriac (SM) es una complicación rara de la diabetes mellitus de tipo 1 (DM1), relacionada con bajas concentraciones de insulina, y es menos común desde que están disponibles insulinas de larga duración de acción. Se caracteriza por la hepatomegalia, el retraso del crecimiento y de la pubertad y la elevación de las transaminasas y de los lípidos séricos. El objetivo de este estudio fue la descripción de los pacientes con criterios de SM en una población pediátrica con DM1. * Corresponding author. E-mail address: joanamprdias@gmail.com (J. Dias).2173-5093/$ -see front matter © 2012 SEEN. Published by Elsevier España, S.L. All rights reserved. J. Dias et al.Material y métodos: Análisis retrospectivo de una población pediátrica diabética atendida en el Hospital de Braga con criterios diagnósticos de SM. Resultados: De una población de 91 pacientes con DM1 menores de 18 años fueron identificados 6 pacientes con criterios de SM: 5 mujeres y un varón. La edad de presentación fue de 13 a 17 años con un intervalo mínimo entre el diagnóstico de DM1 y SM de 4 años. Todos los pacientes tenían prescrita una terapia insulínica intensiva (dosis media diaria: 0,88 U/kg). Todos tenían una historia previa de mal control glucémico a...

Background/objective: Mauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS. Materials and methods:A retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed. Results: From a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13---17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia. Conclusions: Although MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control. © 2012 SEEN. Published by Elsevier España, S.L. All rights reserved. PALABRAS CLAVESíndrome de Mauriac; Diabetes mellitus; Adolescencia El síndrome de Mauriac todavía existeResumen Introducción/objetivo: El síndrome de Mauriac (SM) es una complicación rara de la diabetes mellitus de tipo 1 (DM1), relacionada con bajas concentraciones de insulina, y es menos común desde que están disponibles insulinas de larga duración de acción. Se caracteriza por la hepatomegalia, el retraso del crecimiento y de la pubertad y la elevación de las transaminasas y de los lípidos séricos. El objetivo de este estudio fue la descripción de los pacientes con criterios de SM en una población pediátrica con DM1. * Corresponding author. E-mail address: joanamprdias@gmail.com (J. Dias).2173-5093/$ -see front matter © 2012 SEEN. Published by Elsevier España, S.L. All rights reserved. J. Dias et al.Material y métodos: Análisis retrospectivo de una población pediátrica diabética atendida en el Hospital de Braga con criterios diagnósticos de SM. Resultados: De una población de 91 pacientes con DM1 menores de 18 años fueron identificados 6 pacientes con criterios de SM: 5 mujeres y un varón. La edad de presentación fue de 13 a 17 años con un intervalo mínimo entre el diagnóstico de DM1 y SM de 4 años. Todos los pacientes tenían prescrita una terapia insulínica intensiva (dosis media diaria: 0,88 U/kg). Todos tenían una historia previa de mal control glucémico a...

We report a neonatal case of systemic pseudohypoaldosteronism type 1 caused by a novel mutation in the SCNN1A gene (homozygous c.1052 + 2dupT in intron 3) in which the patient presented with life-threatening hyperkalemia, hyponatremia and metabolic acidosis. It remains uncertain if there is genotype---phenotype correlation, due to the rarity of the disease. This mutation, which to our best knowledge has not been described before, was associated with a very severe phenotype requiring aggressive therapy. © 2012 SEEN. Published by Elsevier España, S.L. All rights reserved. PALABRAS CLAVEPseudohipoaldosteronismo sistémico tipo 1; Hiperpotasemia; Hiponatremia; Acidosis metabólica; Gen SCNN1A Un caso de pseudohipoaldosteronismo sistémico con una mutación nueva en el gen SCNN1AResumen Se presenta un caso neonatal de pseudohipoaldosteronismo sistémico tipo 1 causado por una nueva mutación en el gen SCNN1A (homocigotos C.1052 2 dupT en el intrón 3) en el que el se evidenció hiperpotasemia potencialmente mortal, hiponatremia y acidosis metabólica. Continúa sin saberse con certeza si hay correlación genotipo-fenotipo, debido a la rareza de la enfermedad. Esta mutación, que no ha sido previamente descrita, se asoció con un fenotipo muy grave por lo que requirió un abordaje terapéutico agresivo.

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T>C, GCK c.563C>G, HNF1A c.1623G>A, HNF1A c.1729C>G, HNF4A c.68delG, HNF4A c.422G>C, HNF4A c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals.

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