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.

[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.

[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.

[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.

[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.