Introduction: Autoimmune polyendocrine syndrome type I (APS-1) also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic autosomal recessive disease known by the triad of the major components hypoparathyroidism, primary adrenocortical insufficiency and chronic mucocutaneous candidosis. However, many minor diseases could be present such as other endocrine manifestations (gonadal insufficiency, DM type 1, thyroid disease, pituitary failure), gastrointestinal manifestations (autoimmune gastritis, autoimmune hepatitis, intestinal dysfunction), ectodermal manifestations and others.
Patients and Methods: two siblings affected by APECED with the same genotype (AIRE 260 T>C; 967-979 del) and extremely different phenotypes were compared. Hypoparathyroidism and alopecia were the only two components they have in common. Both siblings have been treated for > 5 years with off label rh-Teriparatide treatment with a good response of calcium levels. The girl (patient 1) showed growth and pubertal delay, vitiligo and ectodermal dystrophy. At the age of 12 chronic diarrhea, abdominal pain and malabsorption appeared. Esophagogastroduodenoscopy showed autoimmune enteropathy characterized by the loss of enteroendocrine cells (EEC) in the gastrointestinal tract. An experimental immunosuppressive therapy with oral Budesonide improved symptoms.
Conversely the brother (patient 2) showed a different phenotype: hypoparathyroidism, primary adrenocortical insufficiency and alopecia were present. Replacement therapy with mineralocorticoid (fludrocortisone) and glucocorticoid (hydrocortisone) was necessary. No growth nor pubertal delay and gastrointestinal symptoms were revealed.
Conclusion: APECED is a multi-systemic disease and it requires a multidisciplinary approach. Hypoparathyroidism can be treated with rh-Teriparatide which seems to be a safe and an effective long-term therapy. Replacement therapy is also necessary when adrenal insufficiency appears. Chronic diarrhea may be due to several causes such as pancreatic exocrine insufficiency (PEI), autoimmune enteropathy (AE), lactose intolerance and celiac disease as well as the same hypocalcemia. Loss of EEC cells determine the reduction of neuroendocrine hormones and consequently gastrointestinal dysfunction. In this condition immunosuppressive therapy is necessary but there are few data in literature so far.
Therefore, although APECED is a monogenic disease, its expressivity may be extremely wide even harbouring the same genotype within the same family. Major components are well known but "minor" components have to be readily recognized with a continuous follow up because they can have important effects on growth and quality of life.
Keywords: Autoimmune polyglandular syndrome type 1, APECED, phenotypic variability, enteroendocrine cells, rh- Teriparatide.
19 Sep 2019 - 21 Sep 2019