SAT-241 Hyposplenism and Autoimmune Hepatitis: Rare Complications of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dystrophy (APECED)

Abstract

Abstract Background: APECED is a rare monogenic autosomal recessive syndrome caused by mutation in the AIRE gene located on chromosome 21q22.3. Phenotypic expression is variable but classically includes chronic mucocutaneous candidiasis, chronic hypoparathyroidism and hypoadrenalism. Studies demonstrate prevalence of autoimmune hepatitis (AIH) is 12%, and hyposplenism is approximately 20%. (Peterson P, Pitkänen J, Sillanpää N,2004; Capalbo D, De Martino L, Giardino G, 2012) Clinical Case: A 29 year old man was diagnosed with autoimmune hepatitis (AIH) at 6 years. He presented with symptomatic hypocalcaemia secondary to autoimmune hypoparathyroidism at 11 years. At 12 years he developed primary adrenal insufficiency. He also had nail dystrophy and mucocutaneous candidiasis. Genetic analysis revealed he was homozygous for for a 13bp deletion in Exon 8 of the AIRE gene consistent with diagnosis of APECED. His sister, who presented with hypoparathyroidism, was also AIRE gene positive. He transitioned from paediatric to adult care age at 16 years and subsequently defaulted from care. Following re-engagement with adult services at age 19 years, he was diagnosed with cirrhosis and portal hypertension and has had an oesophageal variceal bleed. Regular dental review has not revealed an oral mucocutaneous malignancy. At age 24, during an admission with decompensated liver disease, an elevated LDH 384 I.U. /l (120 - 220) and bilirubin (total) 121 μmol/l (5-24) were noted. A blood film demonstrated Howell Jolly bodies, target cells, polychromasia, target cells and anisopoikilocytosis consistent with hyposplenism. In 2011 a CT abdomen reported the spleen as severely shrunken. On review of previous abdominal ultrasounds reports in dating back to 2012 the spleen was undetectable. He was therefore diagnosed with functional hyposplenism. Hyposplenism was complicated by streptococcal sepsis. He was treated as per guidelines with pneumococcus, haemophilus, meningitis C, influenza vaccinations and penicillin prophylaxis. The pathogenesis underlying functional hyposplenism in APECED is unknown however it is hypothesized that it occurs secondary to local AIRE gene dysfunction in the spleen.(Starzyk J, Kumorowicz-Kopiec M, Kowalczyk M, 2001). Another possible contributory factor in this gentleman is his liver cirrhosis. Discussion: This case highlights the multifaceted nature of this rare disease as well as the associated morbidity and need for a multidisciplinary approach to a complex multi-organ condition. It is important to be cognisant of its many associations in order to avoid missing life threatening diagnoses. Patients with APECED should be evaluated for hyposplenia and appropriate vaccination schedule initiated.