Clinical Characteristics in the Longitudinal Follow-Up of APECED Syndrome in Southern Croatia—Case Series

Abstract

Background: Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare monogenetic autosomal recessive disorder caused by a mutation in the autoimmune regulator (AIRE) gene characterized by complex phenotypic characteristics discovered over years of follow-up. Methods: 7 patients were recruited in this case series in a period of the last 37 years from Southern Croatia. All patients were screened for AIRE R257X mutations. Results: This study group had a mean current age of 25.3 years (age range from 5.4 to 40.2 years), while the mean age at the onset of the disease was 6.5 years (age range from 0.7 to 9.2 years) and with a mean follow-up period of 17.8 years. The overall prevalence of APECED syndrome is estimated to be 1 in 75,000. The most common initial manifestation of the disease was onychodystrophy, while the first major component of APECED syndrome was chronic mucocutaneous candidiasis. Conclusions: APECED is a ‘‘multi-faced’’ disease based on the very unpredictable and inconsistent onset of major components. Furthermore, based on our results, we suggest that onychodystrophy could be included as a warning sign of APECED syndrome.

Cutaneous Manifestations in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED): A Comprehensive Review

“…Moreover, an increased occurrence with age was also shown in a prospective study on 158 Italian patients conducted by Garelli, with 51.3% at onset and 74.7% at the end of the follow-up [41]. Finally, a recent observational study conducted on 7 Croatian patients with APS-1 by Skrabic et al, showed a prevalence of 57.1% of CMC [42]. In contrast, a survey conducted by Zlotogora et al in 1992 on a Jewish Iranian population of 23 patients with APS-1 identified a significantly lower prevalence of CMC (17%) [31].…”

“…This data is supported by multiple studies conducted on different populations. Results have shown that chronic mucocutaneous candidiasis was exhibited in APS-1 patients from Finnish, Irish, Saudi Arabian, Italian, North American, Croatian, and Norwegian populations, with a prevalence between 51.3% and 100% [13,[30][31][32][33][34][35][36][37][38][39][40][41][42]. A retrospective study conducted by Ahonen et al between 1910Ahonen et al between -1988 on 68 Finnish patients previously diagnosed with APECED, showed that 100% had a type of CMC [30].…”

Addison’s Disease: Diagnosis and Management Strategies

“… 108 A small study on 7 patients with APS-1 (Southern Croatia) evaluated AIRE R257X mutations; the patients, who were followed for 17.8 years, had an average age at APS onset of 6.5 years. 109 One study on APS-1 (11 patients from unrelated families of Iranian non-Jewish origin) identified 2 novel mutations: homozygous (c.308–1G>C), and a combination of 2 heterozygotes (c.1496delC + c.232T>C). 110 A post-mortem study on a potential eye donor with APS-1 harboring a mutation at R257X (C to T substitution) at exon 6 showed pigmentary deposits at the level of inner retinal vessels causing retinal atrophy, thus confirming retinitis pigmentosa as part of an APS-AD picture.…”

Gastrointestinal manifestations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patient: major effect on treatment and prognosis

“…There is a high heterogeneity of mutations of the AIRE gene, which can vary between different regions within the same country. The R257X mutation of the AIRE gene is the most common mutation in the population of eastern and central Europe ( 4 ).…”