ESPE Abstracts (2019) 92 P1-247

One AIRE Gene Mutation and Two Different Clinical Manifestations in a Couple of Brothers

Tiziana Timpanaro1, Carla Bizzarri2, Alessandra Sauna1, Manuela Caruso-Nicoletti1


1Centro di Endocrinologia e Diabetologia Pediatrica; AOU Policlinico-Vittorio Emanuele, Catania, Italy. 2DPUO; OBG Roma, Roma, Italy


Autoimmune polyglandular syndrome type 1 (APS-1) is also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Clinical manifestations are widely variable. It is an autoimmune disease which is characterized by the triad hypoparathyroidism, Addison disease, and chronic mucocutaneous candidiasis. However, several other autoimmune disorders, not necessarily endocrinological, differing in number and severity, may be present. APS1 is mostly caused by mutations in the autoimmune regulator (AIRE) gene located on chromosome 21q22.

We present the case of two brothers diagnosed with APS-1; molecular analysis revealed a compound heterozygosity for the AIRE gene (c. 415C>T; 967-979 del p r139* L323Sfs* 51 frequently reported in literature) in both. However, they showed very different signs and symptoms at onset.

The older brother was diagnosed at 11 years old after presenting with psoriasis, recurrent mucosal and cutaneous candidiasis since infancy, adrenal insufficiency and hypoparathyroidism. In therapy with rGH for pituitary hypoplasia.

The younger brother presented oral fungal infections and onychomicosis since the very first months of life. At the age of 8 years he showed chronic abdominal pain that led to the finding of hypertransaminasemia.

Workup for hepatitis A, B, C, and Epstein–Barr viruses had yielded no signs of active infection. Anti-gliadin and anti-tissue transglutaminase IgA as well as anti-kidney-liver microsomal and anti-smooth muscle antibodies were negative. A liver biopsy demonstrated severe lympho-histiocytic infiltrate in the portal tracts with moderate interface hepatitis. Treatment with oral prednisone was recently started.

Autoimmune hepatitis is present in 15- 20% of patients with APS-1 and it's rarely the presenting clinical manifestation. Typically, presents with elevated levels of AST and ALT. Treatment requires immunosuppression with the use of glucocorticoids.

As suggested by current literature, clinical APS1 presentation is extremely variable, with poor genotype-phenotype correlation; the two brothers reported show the same genotype, however one of them presented with typical APS-1 triade while the second presented the mucocutaneous candidiasis associated with the extremely rare autoimmune hepatitis.

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