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.
Servio de Endocrinologia, Hospital Central do Funchal, Portugal.
Eduarda
E
Resende
Servicio de Pediatrίa, Hospital Clίnico de Ourense, Spain.
Gemma Novoa
GN
Gόmez
Servio de Pediatria, Hospital Pedro Hispano, Matosinhos, Portugal.
Marta
M
Nascimento
Fundaciόn Pública Galega de Medicina Xenόmica, Santiago de Compostela, Spain.
Lourdes
L
Loidi
Departamento de Pediatrίa, Hospital Clίnico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Rebeca
R
Saborido Fiaño
Unidad de Endocrinologίa Pediátrica y Crecimiento, Departamento de Pediatrίa, Hospital Clίnico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela; Santiago de Compostela, Spain.
Paloma
P
Cabanas Rodrίguez
Unidad de Endocrinologίa Pediátrica y Crecimiento, Departamento de Pediatrίa, Hospital Clίnico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela; Santiago de Compostela, Spain.
Lidia
L
Castro-Feijoo
Unidad de Endocrinologίa Pediátrica y Crecimiento, Departamento de Pediatrίa, Hospital Clίnico Universitario de Santiago de Compostela, Universidad de Santiago de Compostela; Santiago de Compostela, Spain.
Jesús
J
Barreiro Conde
D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein