[Management guidelines for disorders / different sex development (DSD)]. / Guía de actuación en las anomalías de la diferenciación sexual (ADS) / desarrollo sexual diferente (DSD).

Disorders of Sex Development (DSD) include a wide range of anomalies among the chromosomal, gonadal, and phenotypic (genital) characteristics that define sexual differentiation. At present, a definition as Different Sexual Development (DSD) is currently preferred. They originate in the pre-natal stage, are classified according to the sex chromosomes present in the karyotype. The known genetic causes are numerous and heterogeneous, although, in some cases, they may be secondary to maternal factors and/or exposure to endocrine-disrupting chemicals (EDCs). The diagnosis and treatment of DSD always requires multidisciplinary medical and psychosocial care. An aetiological diagnosis needs the interaction of clinical, biochemical (hormonal), genetic, imaging and, sometimes, surgical examinations. The treatment should deal with sex assignment, the possible need for hormone replacement therapy (adrenal if adrenal function is impaired, and with sex steroids from pubertal age if gonadal function is impaired), as well as the need for surgery on genital structures (currently deferred when possible) and/or on gonads (depending on the risk of malignancy), the need of psychosocial support and, finally, an adequate organisation of the transition to adult medical specialties. Patient Support Groups have a fundamental role in the support of families, as well as the interaction with professional and social media. The use of Registries and the collaboration between professionals in Working Groups of national and international medical societies are crucial for improving the diagnostic and therapeutic tools required for the care of patients with DSD.

Precocious presentation of autoimmune polyglandular syndrome type 2 associated with an AIRE mutation.

Autoimmune polyglandular syndrome type 2 (type 2 APS), or Schmidt's syndrome, is defined by the presence of Addison's disease in combination with type 1 diabetes and/or autoimmune thyroid disease. The estimated prevalence of this syndrome is 1.4-4.5 per 100,000 inhabitants and it is more frequent in middle-aged females, whilst it is quite rare in children. Type 2 APS, which shows a pattern of autosomal dominant inheritance with low penetrance, has been associated with HLA specific DR3/DQ2 and DR4/DQ8 haplotypes. However, it has been hypothesized that genetic variability in the AIRE gene, which causing type 1 APS, may play a role in more common organ-specific autoimmune conditions like type 1 diabetes, Hashimoto's disease and type 2 APS, among others. Here we present the case of an 8-year-old girl, with a past medical history of type 1 diabetes diagnosed at the age of 3. She was taken to the Emergency Department because she complained of abdominal pain, nausea and vomiting, and her blood analysis revealed a severe hyponatremia. She also had seizures as a consequence of the hyponatremia and frequent hypoglycemia. She was ultimately found to be suffering from autoimmune primary adrenal insufficiency. The combination of both mentioned conditions, type 1 diabetes and Addison's disease, in the absence of chronic mucocutaneous candidiasis, made a diagnosis of type 2 APS plausible in this girl. The genetic study showed two heterozygous variants: NM_000383.2:C.1411C>T (p. Arg471Cys) in exon 12 and IVS9+6G>A in intron 9 of the AIRE gene. The description of an uncommon case of type 2 APS with precocious presentation associated with an AIRE mutation in a very young girl could help to clarify the role of AIRE in the development of autoimmune diseases.