Growth patterns and outcomes of growth hormone therapy in patients with acrodysostosis.

INTRODUCTION: Severe short stature is a feature of acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations). METHODS: We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5. RESULTS: We included 20 and 17 individuals with iPPSD4 and iPPSD5, respectively. The rhGH-treated iPPSD4 patients (n = 9) were smaller at birth than those who did not receive rhGH (median - 2.2 SDS vs. - 1.7 SDS); they showed a trend to catch-up growth during rhGH therapy (median 0.5 SDS in the first year). The rhGH-treated patients (n = 5) reached a better final height compared to those who did not receive rhGH (n = 4) (median - 2.8 SDS vs. - 3.9 SDS), suggesting that rhGH is efficient to increase height in those patients. The difference in target height to final height ranged between 1.6 and 3.0 SDS for iPPSD4 not treated with rhGH (n = 4), 2.1-2.8 SDS for rhGH-treated iPPSD4 (n = 5), 0.6-5.5 SDS for iPPSD5 not treated with rhGH (n = 5) and 2.5-3.1 for rhGH-treated iPPSD5 (n = 2). CONCLUSION: Final height may be positively influenced by rhGH in patients with acrodysostosis/iPPSD. Our rhGH-treated cohort started therapy relatively late, which might explain, at least in part, the limited effect of rhGH on height.

Seguimiento clínico y autocuidados en niños y adolescentes con posibles secuelas endocrinológicas tras el cáncer: pasaporte de salud para supervivientes / Clinical follow-up and self-care in children and adolescents with possible endocrinological sequelae after cancer: passport of healthcare for survivors

El tratamiento del cáncer en los niños y adolescentes hamejorado la supervivencia de manera espectacular en losúltimos 30 años. Ahora nos enfrentamos al reto de cuidara estos pacientes, para mejorar su calidad de vida a largoplazo. Esto incluye diagnosticar precozmente los efectos tardíos de los tratamientos que pueden ocurrir en la mayoríade los pacientes supervivientes del cáncer y en concreto ennuestro caso, de los efectos endocrinológicos, que son muyfrecuentes.Se han descrito los efectos endocrinos de quimioterápicos, de la radioterapia, y debemos controlar la aparición deotros, tras el empleo de agentes nuevos en el tratamiento delcáncer, como inmunoterápicos, lo que obliga a monitorizara estos pacientes de forma estrecha.La radioterapia y los agentes alquilantes, muy gonadotóxicos, son el principal factor de riesgo para el desarrollo deefectos tardíos endocrinos. Los glucocorticoides sistémicosa dosis altas pueden afectar a la mineralización ósea y almetabolismo. Nuevos tratamientos como los inhibidores dela tirosin-kinasa y los inmunomoduladores se han descritoque afectan de manera particular al tiroides y a la hipófisis.El seguimiento de los pacientes debe hacerse basado enel riesgo de aparición de los efectos, y en este artículo describimos nuestra propuesta de la atención endocrinológica.Una detallada información sobre el tratamiento del cáncer ylos posibles riesgos futuros, dada de forma progresiva a lospacientes, y ofrecida según su madurez, no debe obviarse, ypuede y debe ser una herramienta que les ayude a conseguirsu mayor salud posible. Hemos de utilizar guías médicasbasadas en la evidencia, y ofrecer documentación disponible para pacientes, que contribuyan a formar e informar alpaciente sobre sus riesgos. Cada centro habrá de organizarsede la mejor manera posible, siendo imprescindible una buenacolaboración multidisciplinar(AU)

Incidencia de diabetes tipo 1 en Navarra (2009-2016): mayor en la zona sur de la comunidad / Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern regions of the autonomous community

Fundamento: Las variaciones geográficas y estacionales en la incidencia de diabetes tipo 1 (DM1) son útiles para intentar conocer la etiopatogenia de la enfermedad. El objetivo de este estudio consiste en conocer los datos de incidencia de DM1 en Navarra durante el período 2009-2016, su distribución geográfica y su variación en cuanto a la estación del año en la que tiene lugar tanto el nacimiento como el diagnóstico de las personas afectadas. Métodos: Estudio prospectivo, con una fuente primaria y tres secundarias. La exhaustividad del registro se evaluó mediante el método de captura-recaptura y fue del 96,08%. La estimación de las tasas e intervalos de confianza al 95% por zonas y estaciones al debut se realizó asumiendo una distribución subyacente de Poisson. La influencia independiente de las variables edad al debut, sexo, zonas y estaciones del año, se estudió mediante la regresión de Poisson. Para la comparación de la incidencia interregional, los valores obtenidos se ajustaron por el método de estandarización indirecta. Resultados: Se detectaron 428 casos (incidencia= 8,36/100.000 habitantes-año; IC95%: 7,58-9,19). La enfermedad predomina en hombres (63%). La incidencia en menores de 15 años fue mayor que en los adultos (21,54; IC95%: 18,43-25,02 vs. 5,94; IC95%: 5,23-6,71; p<0,001). Se observa mayor incidencia en las cuatro regiones del sur de la Comunidad Foral, y en invierno y primavera como estaciones al debut. No hay diferencias en la estación al nacimiento. Conclusión: Navarra mantiene una alta incidencia de DM1 en la infancia que va disminuyendo progresivamente con la edad. Se detectan diferencias por sexo, edad, zona geográfica y estación al diagnóstico (AU)

Background: Geographical and seasonal variations of type 1 diabetes (T1D) are useful for establishing the key ethiopathogenic factors of the disease. The present work seeks to analyze the incidence rates of T1D in Navarre for the 2009-2016 period, its geographical distribution and seasonal variations in birth and diagnosis in affected persons. Methods: Prospective study with one primary and three secondary sources. The completeness of the registry, determined using the capture-recapture method, was 96.08%. The confidence intervals of zone and onset season incidence rates were determined assuming an underlying Poisson distribution. Adjusted effect of onset age, sex, onset season and geographical area over changes in incidence rates were analyzed using a Poisson regression model. Comparison among areas was carried out after the corresponding adjustments of incidence by the indirect standardization method. Results: Four hundred and twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients). The incidence in children under 15 years was higher than in adults (21.54, CI95%: 18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the four southern regions of Navarre, most of the cases being in winter and spring. No differences were found regarding birth season over incidence. Conclusion: Navarre maintains a high T1D incidence in childhood that decreases progressively with age. Sex, age group, geographical zone and onset season are independently associated with the incidence rates observed in the study (AU)

[Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern regions of the autonomous community]. / Incidencia de diabetes tipo 1 en Navarra (2009-2016): mayor en la zona sur de la comunidad.

BACKGROUND: Geographical and seasonal variations of type 1 diabetes (T1D) are useful for establishing the key ethio-pathogenic factors of the disease. The present work seeks to analyze the incidence rates of T1D in Navarre for the 2009-2016 period, its geographical distribution and seasonal variations in birth and diagnosis in affected persons. METHODS: Prospective study with one primary and three secondary sources. The completeness of the registry, determined using the capture-recapture method, was 96.08%. The confidence intervals of zone and onset season incidence rates were determined assuming an underlying Poisson distribution. Adjusted effect of onset age, sex, onset season and geographical area over changes in incidence rates were analyzed using a Poisson regression model. Comparison among areas was carried out after the corresponding adjustments of incidence by the indirect standardization method. RESULTS: Four hundred and twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients). The incidence in children under 15 years was higher than in adults (21.54, CI95%: 18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the four southern regions of Navarre, most of the cases being in winter and spring. No differences were found regarding birth season over incidence. CONCLUSION: Navarre maintains a high T1D incidence in childhood that decreases progressively with age. Sex, age group, geographical zone and onset season are independently associated with the incidence rates observed in the study.

[Low height and rare diseases]. / Talla baja y enfermedades raras.

Low stature is the main reason of consultation in paediatric endocrinology. In a high percentage of cases, its etiology is clear and fundamentally answers to variants of normality. However, in approximately 20% of cases low stature is pathological and requires exhaustive studies. The association of rare diseases (RD) with low height is very frequent. In this article we review the etiology of low height, describing: - The genetic forms of the growth hormone (GH), whether isolated or associated with malformations of the average line or others. - Those which are of great importance due to their clinical repercussion, such as Turner's Syndrome, Noonan's Syndrome and Willi-Prader's Syndrome. - The frequent osseous dysplasias, in some cases with genetic alterations of the SHOX gene, situated in the short arm of the Xp chromosome. The importance of these diagnoses lies in the possibility of carrying out early and efficient treatment, in some of them, with GH. In conclusion, the diagnosis of rare diseases with low height is a current and normal challenge in paediatric endocrinology due to the great advances in molecular genetics and the possibility of treatment in some of them. It always involves a multidisciplinary approach due to the frequent association of pathology it presents, and, in its turn, it offers the possibility of carrying out timely genetic counselling.

Talla baja y enfermedades raras / Low height and rare diseases

La baja talla constituye el primer motivo de consultaen endocrinología pediátrica. En un alto porcentajesu etiología es clara y obedece fundamentalmentea variantes de normalidad. Sin embargo, en aproximadamenteun 20% esta baja talla es patológica y obliga aestudios exhaustivos.La asociación de enfermedades raras (ER) con tallabaja es altamente frecuente. En este trabajo repasamoslas etiologías de la baja talla en enfermedades raras,describiendo:– las formas genéticas de la hormona de crecimiento(GH) bien sean aisladas o asociadas amalformaciones de la línea media u otras.– aquellas de gran importancia por su repercusiónclínica como el Síndrome de Turner, Síndromede Noonan y el Síndrome de Willi-Prader.– Las frecuentes displasias óseas, con alteracióngenética en algunos casos para el gen SHOX,situado en el brazo corto del cromosoma Xp.La importancia de estos diagnósticos radica en laposibilidad de hacer un tratamiento precoz y eficaz, enalgunos de ellos, con GH.En conclusión, el diagnóstico de enfermedadesraras con baja talla es un reto actual y habitual en endocrinologíapediátrica por los grandes avances de lagenética molecular y la posibilidad de tratamiento enalgunas de ellas. Implica siempre un abordaje multidisciplinariopor la asociación frecuente de patología quepresenta y a su vez, ofrece la posibilidad de realizar eloportuno consejo genético

Low stature is the main reason of consultation inpaediatric endocrinology. In a high percentage of cases,its etiology is clear and fundamentally answers tovariants of normality. However, in approximately 20% ofcases low stature is pathological and requiresexhaustive studies.The association of rare diseases (RD) with lowheight is very frequent. In this article we review theetiology of low height, describing:– The genetic forms of the growth hormone(GH), whether isolated or associated withmalformations of the average line or others.– Those which are of great importance due totheir clinical repercussion, such as Turner’sSyndrome, Noonan’s Syndrome and Willi-Prader’s Syndrome.– The frequent osseous dysplasias, in somecases with genetic alterations of the SHOXgene, situated in the short arm of the Xpchromosome.The importance of these diagnoses lies in thepossibility of carrying out early and efficient treatment,in some of them, with GH.In conclusion, the diagnosis of rare diseases withlow height is a current and normal challenge inpaediatric endocrinology due to the great advances inmolecular genetics and the possibility of treatment insome of them. It always involves a multidisciplinaryapproach due to the frequent association of pathologyit presents, and, in its turn, it offers the possibility of carrying out timely genetic counselling

[Familial benign partial epilepsy of early infancy]. / Epilepsia parcial benigna familiar de la infancia temprana.

INTRODUCTION AND CLINICAL CASES: We present two patients who at the ages of 5 and 17 months respectively presented with convulsive crises with motor signs, of partial onset and secondary generalization, which eventually became normal. Both patients had a family history of first degree relatives with similar illnesses and are at present-five years later-well and with normal development, school achievement and neurological examination findings. The clinical characteristics, normal biochemical and neuroimaging investigations and EEG characteristics suggest the diagnosis of benign partial epilepsy of early infancy. This syndrome is characterized by its appearance during the first year of life, having no known etiological factors, with partial crises occurring several times a day and with a course leading to remission. Its frequency may be greater than is thought. There is a pattern of dominant autosomal inheritance, with a gene recently found on chromosome 19. CONCLUSION: We consider that this syndrome should be included in the International Classification of Epilepsy and Epileptic Syndromes as benign familial idiopathic partial epilepsy.

[Andermann syndrome: presentation of a case]. / Síndrome de Andermann. Presentación de un caso.

INTRODUCTION: Peripheral neuropathy with agenesis of the corpus callosum (or Andermann's syndrome) is a hereditary autosomal recessive disorder rarely found outside certain regions of Quebec Province (Canada). It is associated with mental retardation and various dysmorphic changes. Deterioration is usually progressive with loss of motor skills, development of scoliosis during adolescence, tendency to behaviour disorders and death during the third decade (approximately). CLINICAL CASE: We present a 13 year old girl diagnosed as having the spastic tetraparesic type of PCI, who was sent to us so that we could reconsider the diagnosis in view of the atypical course of the illness. The patient had an unusual phenotype with dysmorphic changes (mainly facial), axial hypotonia with flexion-retraction of the hands, generalized arreflexia, neurogenic bladder, skin changes with ulcers on the legs and mental retardation. Neurophysiological studies showed a predominantly motor polyneuropathy. There were signs of axonal neuropathy on both sural nerve and skeletal muscle biopsies. The clinical features, phenotype, microcephaly with agenesis of the corpus callosum and a posterior fossa cyst, associated with spinal atrophy indicated the diagnosis of Andermann's syndrome. CONCLUSIONS: This case is of interest in view of the exceptional rarity of Andermann's syndrome in our population.