Unidad de Endocrinología Pediátrica y Diabetes del Hospital Infantil Universitario Miguel Servet: de nuestro pasado, presente y futuro / Pediatric endocrinology and diabetes unit of the Hospital Infantil Universitario Miguel Servet: our past, present and future

La endocrinología pediátrica es un área específica de la pediatría en constante evolución que ha experimentado un gran desarrollo en los últimos 30 años. En este trabajo se presenta el desarrollo de la Unidad de Endocrinología Pediatrica y Diabetes del Hospital Infantil Miguel Servet de Zaragoza desde su creación en 1978. La Unidad realiza una importante labor asistencial, docente y de investigación clínica, tanto en el campo de la endocrinología como de la diabetes y la cartera de servicios incluye los trastornos endocrinos desde la edad fetal hasta la adolescencia. La Unidad ha tenido una especial dedicación al crecimiento normal y patológico, elaboración de estándares de referencia y a la detección precoz de las endocrinopatías infantiles, actuando como centro de referencia en el cribado neonatal (AU)

Pediatric endocrinology is a specific pediatric subespeciality in permanent evolution that has experienced a tremendous development in the last 30 years. In this article the evolution of the Pediatric Endocrinology and Diabetes Unit of the Children’s Hospital Miguel Servet is presented since it was created in 1978. The Unit displays an important medical activity in terms of assistance, teaching and clinical research, both in the field of endocrinology and diabetes, and it attends all endocrinopathies since fetal period until adolescence. The Unit has been specially focused on normal and abnormal growth and development, elaboration of growth standards and early detection of pediatric endocrinopathies being a center of reference in neonatal screening (AU)

[Type 1 polyglandular autoimmune syndrome associated with C322fsx372 mutation]. / Síndrome poliglandular autoinmune tipo 1 y mutación C322fsX372.

Polyglandular autoimmune syndromes are rare diseases based on autoimmune mechanisms in which endocrine and non-endocrine disorders coexist. In type 1 the characteristic manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. A case is presented of a patient with typical clinical sequence, along with other changes, and in whom a mutation in homozygosis, C322fsX372, was detected after performing a molecular analysis of autoimmunity regulator gene (AIRE). Inheritance is autosomal recessive, associated with mutations in the AIRE gene, which encodes a protein involved in autoimmunity and immunodeficiency. For diagnosis, At least two of the three major clinical manifestations are required for a diagnosis. However, only one of them is necessary in the study of relatives of affected patients. These syndromes must be diagnosed early, given their high morbidity and mortality. Every manifestation needs to be treated, in order to maintain the quality of life.

[Wolfram syndrome. Clinical and genetic study in two families]. / Síndrome de Wolfram. Estudio clínico y genético en dos familias.

Wolfram syndrome (WS), also known as DIDMOAD (due to its association with diabetes insipidus, diabetes mellitus, optic atrophy and deafness), is an infrequent cause of diabetes mellitus. This syndrome is included among the genetic disorders associated with diabetes in the American Diabetes Association's classification. WS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders and gonadal disorders. The most frequent of these disorders is early onset diabetes mellitus, with a low prevalence of ketoacidosis, and optic atrophy, which is considered a key diagnostic criterion in this syndrome. Diabetes insipidus usually develops later. This syndrome manifests in childhood, hampering diagnosis and treatment. Morbidity and mortality are high and quality of life is impaired due to neurological and urological complications. This article describes the clinical characteristics and outcome in three patients with WS. All three patients had antecedents of consanguinity. Genetic study was performed in all patients. One was homozygotic for the WFS1 gene that encodes the WFS1 G736A mutation in exon 8 and the remaining two patients, who were siblings, were homozygotic for the 425ins16 mutation in exon 4.

Síndrome de Wolfram. Estudio clínico y genético en dos familias / Wolfram syndrome. Clinical and genetic study in two families

El síndrome de Wolfram, también conocido con la denominación DIDMOAD (por asociar diabetes insípida, diabetes mellitus [DM], atrofia óptica y sordera), es una causa muy poco frecuente de diabetes mellitus. Se encuentra dentro de los síndromes genéticos que pueden asociarse con diabetes en la clasificación de la American Diabetes Association (ADA). Es un cuadro neurodegenerativo con transmisión autosómica recesiva. Cursa con diversas manifestaciones clínicas, como la DM, la atrofia óptica, la diabetes insípida (DI), la sordera, la dilatación de las vías urinarias, alteraciones en el sistema nervioso central, alteraciones psiquiátricas y alteraciones gonadales; entre las más frecuentes destaca la DM, que es de aparición precoz y con poca prevalencia de cetoacidosis, y la atrofia óptica, la cual se considera el criterio diagnóstico fundamental en este síndrome. La DI suele aparecer más tarde. Este síndrome se presenta en la infancia, lo que da lugar a una mayor dificultad diagnóstica y terapéutica, con una elevada morbimortalidad y deterioro de la calidad de vida por las afectaciones neurológicas y urológicas. En el presente artículo describimos las características clínicas de 3 pacientes con síndrome de Wolfram y su evolución. En todos ellos existían antecedentes de consanguinidad. Se practicó análisis genético en los tres casos, uno presentó en homocigosis la mutación del gen WFS1 G736A en el exón 8, y los otros dos, que eran hermanos, homocigosis con la mutación del gen 425ins16 en el exón 4

Wolfram syndrome (WS), also known as DIDMOAD (due to its association with diabetes insipidus, diabetes mellitus, optic atrophy and deafness), is an infrequent cause of diabetes mellitus. This syndrome is included among the genetic disorders associated with diabetes in the American Diabetes Association's classification. WS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders and gonadal disorders. The most frequent of these disorders is early onset diabetes mellitus, with a low prevalence of ketoacidosis, and optic atrophy, which is considered a key diagnostic criterion in this syndrome. Diabetes insipidus usually develops later. This syndrome manifests in childhood, hampering diagnosis and treatment. Morbidity and mortality are high and quality of life is impaired due to neurological and urological complications. This article describes the clinical characteristics and outcome in three patients with WS. All three patients had antecedents of consanguinity. Genetic study was performed in all patients. One was homozygotic for the WFS1 gene that encodes the WFS1 G736A mutation in exon 8 and the remaining two patients, who were siblings, were homozygotic for the 425ins16 mutation in exon 4

[Intracraneal hemorrhage caused by neonatal alloimmune thrombocytopenia. Report of a case and review]. / Hemorragia intracraneal por trombopenia neonatal aloinmune. Comunicación de un caso y revisión.

INTRODUCTION: Neonatal alloimmune thrombocytopenia (NAT) is due to the transplacental transfer of circulating maternal alloantibodies developed against fetal platelet antigens inherited from the father. Intracranial hemorrhage occurs in 15-30% of the cases, and very important neurological sequelaes can be due to it. CASE REPORT: We present the clinical and immunohematologic findings of a case of severe NAT that had two siblings who died by this illness. In the 31st week of gestation an intracranial hemorrhage is detected by echography, the birth was by caesarean section. Apgar score of 8 and 9, it wasn't necessary reanimation procedures. Cutaneous purpura and pallor were presented since birth. Neonatal complete blood count showed a platelet count of 6,000/mm3 (whereas maternal blood count was normal), haemoglobin of 8.8 g/dL and hematocrit of 26.1%, without other biological alterations. In maternal blood alloantibodies antiHPA-1a were detected, being the father homozigous for 1a/1a and the mother homozigous for 1b/1b. The patient was treated with transfusions, endovenous gammaglobulin and corticosteroids and his condition improved. CONCLUSIONS: Intraparenchymatous hemorrhage is an uncommon pathology in neonates, but when this occurs it's obligated to rule out a coagulation inherited illness, NTA especially, because of its prevalence and potentially serious neurological sequelaes, sometimes having a good neurological development. Prevention, early treatment and neuroimaging studies should be done in all newborn babies with alloimmune thrombocytopenia even when no neurological clinic is seen.

Hemorragia intracraneal por trombopenia neonatal aloinmune. Comunicación de un caso y revisión / Intracraneal hemorrhage caused by neonatal alloinmune thrombocytopenia. Report of a case and review

Introducción. La trombopenia neonatal aloinmune (TNA)se debe al paso de aloanticuerpos maternos dirigidos contra losantígenos plaquetarios fetales heredados del padre. En un 15-30%de los casos se produce hemorragia cerebromeníngea que puedeconducir a secuelas neurológicas importantes. Caso clínico. Sedescribe un caso de TNA en un recién nacido con antecedentes dedos hermanos fallecidos por el mismo motivo. A las 31 semanas sedetecta por ecografía hemorragia cerebral intraparenquimatosa yse efectúa parto por cesárea. Apgar de 8 y 9, no precisa maniobrasde reanimación. El examen físico revelaba desde el nacimientopúrpura cutánea generalizada y palidez, y el hemograma, una plaquetopeniagrave de 6.000/mm3; el recuento de la madre es normal,hemoglobina de 8,8 g/dL y hematocrito de 26,1%, sin otrasalteraciones biológicas destacables. En la sangre materna se detectaronaloanticuerpos de especificidad anti-HPA-1a; el padre eshomocigoto para 1a/1a, y la madre, para 1b/1b. Recibió transfusionesde plaquetas, así como inmunoglobulina endovenosa y corticoterapia,y evoluciona favorablemente. Conclusiones. La hemorragiaintracraneal parenquimatosa es una patología neonatal pocofrecuente, lo que obliga siempre a descartar un trastorno congénitode la coagulación, especialmente una TNA por su frecuencia ypotencial gravedad; en ocasiones puede tener una buena evoluciónneurológica. Es fundamental su prevención y tratamiento precoz yla realización de estudios de imagen, aun en ausencia de clínicaneurológica

Introduction. Neonatal alloimmune thrombocytopenia (NAT) is due to the transplacental transfer of circulatingmaternal alloantibodies developed against fetal platelet antigens inherited from the father. Intracranial hemorrhage occurs in15-30% of the cases, and very important neurological sequelaes can be due to it. Case report. We present the clinical andimmunohematologic findings of a case of severe NAT that had two siblings who died by this illness. In the 31st week ofgestation an intracranial hemorrhage is detected by echography, the birth was by caesarean section. Apgar score of 8 and 9,it wasn’t necessary reanimation procedures. Cutaneous purpura and pallor were presented since birth. Neonatal completeblood count showed a platelet count of 6,000/mm3 (whereas maternal blood count was normal), haemoglobin of 8.8 g/dL andhematocrit of 26.1%, without other biological alterations. In maternal blood alloantibodies antiHPA-1a were detected, beingthe father homozigous for 1a/1a and the mother homozigous for 1b/1b. The patient was treated with transfusions, endovenousgammaglobulin and corticosteroids and his condition improved. Conclusions. Intraparenchymatous hemorrhage is an uncommonpathology in neonates, but when this occurs it’s obligated to rule out a coagulation inherited illness, NTA especially,because of its prevalence and potentially serious neurological sequelaes, sometimes having a good neurological development.Prevention, early treatment and neuroimaging studies should be done in all newborn babies with alloimmune thrombocytopeniaeven when no neurological clinic is seen