Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study

Abstract

ObjectiveAutoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.DesignTwenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.MethodsClinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.ResultsPatients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.ConclusionsIndian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.

Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy

“… Shown are approximate percentages of corresponding APECED manifestations pooled from various published studies comparing data from the American or other international cohorts …”

“…Earlier diagnosis is critical for a number of reasons. First, several of the autoimmune manifestations in APECED are life‐threatening including adrenal crisis, hypocalcemic seizures, fulminant hepatitis, autoimmune lung disease and pneumococcal sepsis, which collectively account for the increased mortality in these patients . Therefore, earlier diagnosis may allow for earlier screening and recognition of the aforementioned clinical complications.…”

“…First, several of the autoimmune manifestations in APECED are life-threatening including adrenal crisis, hypocalcemic seizures, fulminant hepatitis, autoimmune lung disease and pneumococcal sepsis, which collectively account for the increased mortality in these patients. 7,9,18,40 Therefore, earlier diagnosis may allow for earlier screening and recognition of the aforementioned clinical complications. Second, earlier diagnosis may allow for the institution of prophylactic immunomodulation in children with APECED, which may result in prevention of the development of the full-blown syndrome and its irreversible autoimmune sequelae.…”

Type 3 autoimmune polyendocrine syndrome (APS) diagnosed in an 87-year-old patient with a concomitant chronic autoimmune urticaria

“…syndrome. Moreover, according to various sources the broad spectrum of the disease includes also autoimmune hepatitis, type 1 diabetes, hypothyroidism, hypogonadism, malignant anaemia, asplenism, and alopecia areata [1,3,8,10,11]. APS-2 type (Schmidt's syndrome) is the most common APS phenotype.…”

“…The patient confirmed a history of arterial hypertension that was stable and responded to treatment (for about 20 years; for a cou-W przypadku APS-1 należy się spodziewać triady objawów: przewlekłej kandydozy śluzówek, niedoczynności przytarczyc i kory nadnerczy, jednak do rozpoznania wystarczą 2 spośród 3 wymienionych. Szerokie spektrum schorzenia obejmuje także, według różnych źródeł, autoimmunologiczne zapalenie wątroby, cukrzycę typu 1, niedoczynność tarczycy, hipogonadyzm, anemię złośliwą, asplenizm, łysienie plackowate [1,3,8,10,11]. Typ APS-2 (zespół Schmidta) jest najczęstszym fenotypem APS.…”