Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulatory (AIRE) gene. The classic triad comprises of chronic mucocutaneous candidiasis, hypoparathyroidism and Addison’s disease, however other autoimmune manifestations may occur. Autoimmune metaplastic atrophic gastritis (AMAG) and pernicious anaemia occurs in approximately 16% of patients with APECED (1), which may cause impaired calcium absorption (2,3).
Clinical Case: A 23-year-old female with APECED had known clinical manifestations of hypoparathyroidism, adrenal insufficiency, chronic mucocutaneous candidiasis, and premature ovarian failure. In terms of calcium supplementation, she was taking in total six tablets of calcium carbonate and eight tablets of calcitriol daily. She presented to emergency with symptomatic hypocalcaemia with QT prolongation. She had been mostly adherent with her calcium supplements and had no increased gastrointestinal losses. Initial ionised calcium was 0.89 mmol/L (1.13-1.33 mmol/L), corrected calcium was 1.95 mmol/L (2.10-2.60 mmol/L), magnesium was 0.73 mmol/L (0.7-1.10 mmol/L), phosphate was 2.21 mmol/L (0.75-1.50 mmol/L), parathyroid hormone was <0.01 pmol/L (1.5-7.0 pmol/L), 25-OH vitamin D was 100 nmol/L (50-250 nmol/L), and haemoglobin was 131 g/L (120-160 g/L). She had previous multiple similar presentations with symptomatic hypocalcaemia. It was noted that she had vitamin B12 deficiency two years prior despite non-vegetarian diet and had replacement with injections previously. Retesting revealed low vitamin B12 again with holotranscobalamin level of 24.3 pmol/L (>35.0 pmol/L). Consequently, co-existing AMAG was further investigated for and showed positive intrinsic factor antibodies with a level of >480.0 U/mL (>7 U/mL). Alternative calcium supplementation was explored including calcium citrate, which may have superior absorption than calcium carbonate in patients with achlorhydria and atrophic gastric mucosa (3).
Conclusion: Calcium malabsorption should be considered in APECED patients with hypoparathyroidism presenting with recurrent hypocalcaemia. This case highlights AMAG as an important comorbidity to screen for in this population.