Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomic recessive disease due to AIRE gene mutations, inducing central immune tolerance breakdown. It was poorly known in France.
Objectives: To describe clinical and immunological phenotypes, to determine main genotypes in West Northern France (9 millions inhabitants), to identify factors that could influence phenotypes, and to analyse immunosuppressive therapies indications in APS1.
Methods: Clinical and immunological datas have been collected thanks to West Northern France endocrinologists and paediatricians collaboration. Pathological mutations were identified by DNA sequencing.
Results: About 19 patients (7 females, 12 males, age 31±13 yr) from 13 families have been identified. Clinical manifestations varied greatly among patients, from 1 to 10 components. Candidiasis and adrenal insufficiency frequently occurred in respectively 17 patients (89%) and 15 patients (79%). Surprisingly, hypoparathyroidism was diagnosed in only 12 cases (63%), whereas alopecia was particularly frequent, in 10 patients (53%). In 3 patients presenting with atypical forms, molecular diagnosis confirmation was essential. Four different AIRE gene mutations were identified, and 13bp-deletion in exon 8 (c.967-979del13) was the most prevalent. A correlation between this mutation on at least one allele and alopecia occurrence was identified (P=0.003). There was an elevation of mean CD4+ lymphocytes concentrations (1103±256/mm3) while mean CD8+(412±156/mm3) and CD20+(174±131/mm3) lymphocytes concentrations were diminished, with a mean elevated CD4/CD8 ratio (2.51±1.24). Four patients were treated by immunosuppressive therapies: 2 for hepatitis, one for severe malabsorption and one for a T-cell large granular lymphocytes leukaemia. Those therapies were very efficient but a patient deceased of septicaemia (C. Albicans).
Conclusion: APS1 frequency in West Northern France was about 1/500 000. Phenotypes varied greatly, and molecular diagnosis was determinant in atypical cases. Immunosuppressive therapies remain essential in severe manifestations, but their initiation should be preceded by candidiasis and other infections careful research and treatment.
03 - 07 May 2008
European Society of Endocrinology