POLYENDOCRINOPATHY, CANDIDIASIS, ECTODERMAL DYSTROPHY, KERATOCONJUNCTIVITIS, AUTOIMMUNE HEPATITIS, ADRENAL INSUFFICIENCY AND HYPOPARATHYROIDISM IN AN ADULT FEMALE.

Abstract

Introduction Autoimmune Polyendocrine Syndrome (APS), or Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy (APECED), is a rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE).(1,2) Given the wide variation in clinical presentation, the diagnosis of APS can be challenging and delayed. Case Description We present a 46-year-old female with a history of tetralogy of Fallot, hypoparathyroidism, autoimmune hepatitis status-post liver transplantation, large granular lymphocytic leukemia, recurrent HSV keratitis status-post four corneal transplants, CMV viremia and disseminated histoplasmosis. Genetic testing revealed a normal Microarray with biallelic pathogenic variants in the AIRE gene. The homozygous frameshift variant designated c.967_979del13 (p.Leu323SerfsX51) results in an unstable gene product and appears to be one of the most common mutations in APS(3). This result was diagnostic for APS-1 and provided a cohesive explanation for her keratoconjunctivitis, history of autoimmune hepatitis, adrenal insufficiency and hypoparathyroidism, but not for the congenital heart disease. Genetic testing for known variants of DiGeorge syndrome was negative. Discussion The estimated prevalence of APS-1 is 1:100,000.(4) It is characterized by the development of at least two of three cardinal components: chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency.(4) The syndrome can manifest from early infancy to adulthood, and new components can appear throughout life.(5) Patients have an increased risk of cancer and mortality compared to the general population,(6) which makes early diagnosis key. Because of the clinical variability, our patient's diagnosis was quite delayed. Patients need appropriate multidisciplinary care to help prevent and monitor for end-organ damage with early introduction of appropriate immunomodulatory therapy. Autoimmune Polyendocrine Syndrome (APS), or Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy (APECED), is a rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE).(1,2) Given the wide variation in clinical presentation, the diagnosis of APS can be challenging and delayed. We present a 46-year-old female with a history of tetralogy of Fallot, hypoparathyroidism, autoimmune hepatitis status-post liver transplantation, large granular lymphocytic leukemia, recurrent HSV keratitis status-post four corneal transplants, CMV viremia and disseminated histoplasmosis. Genetic testing revealed a normal Microarray with biallelic pathogenic variants in the AIRE gene. The homozygous frameshift variant designated c.967_979del13 (p.Leu323SerfsX51) results in an unstable gene product and appears to be one of the most common mutations in APS(3). This result was diagnostic for APS-1 and provided a cohesive explanation for her keratoconjunctivitis, history of autoimmune hepatitis, adrenal insufficiency and hypoparathyroidism, but not for the congenital heart disease. Genetic testing for known variants of DiGeorge syndrome was negative. The estimated prevalence of APS-1 is 1:100,000.(4) It is characterized by the development of at least two of three cardinal components: chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency.(4) The syndrome can manifest from early infancy to adulthood, and new components can appear throughout life.(5) Patients have an increased risk of cancer and mortality compared to the general population,(6) which makes early diagnosis key. Because of the clinical variability, our patient's diagnosis was quite delayed. Patients need appropriate multidisciplinary care to help prevent and monitor for end-organ damage with early introduction of appropriate immunomodulatory therapy.