Intracranial Calcifications in Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) Syndrome: A Case Report and Literature Review

Abstract

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED [MIM 240300]), also known as autoimmune polyglandular syndrome type I (APS I), is a rare, debilitating autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. The clinical spectrum of the disease is variable and includes several autoimmune endocrine and non-endocrine manifestations, which may lead to acute metabolic alterations and eventually life-threatening events. The clinical diagnosis requires the presence of two out of three major criteria; chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and autoimmune adrenal failure. Brain calcifications secondary to hypoparathyroidism have been reported in many patients with APECED. These tend to be extensive, bilateral and symmetrical and have characteristic predilection to the basal ganglia. The calcifications may extend to affect the cerebellum and subcortical white matter. The aim of this work is to describe intracranial calcifications in APECED and to report a new feature of pontine calcification expanding the phenotype of this rare condition.

Keywords

APECED - intracranial calcification - pontine calcification - AIRE - autoimmune hypoparathyroidism

• References

• 1 Kisand K, Peterson P. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: known and novel aspects of the syndrome. Ann N Y Acad Sci 2011; 1246: 77-91
• 2 Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 1997; 17 (4) 399-403
• 3 Björses P, Aaltonen J, Vikman A , et al. Genetic homogeneity of autoimmune polyglandular disease type I. Am J Hum Genet 1996; 59 (4) 879-886
• 4 Arstila TP, Jarva H. Human APECED; a Sick Thymus Syndrome?. Front Immunol 2013; 4: 313
• 5 Faiyaz-Ul-Haque M, Bin-Abbas B, Al-Abdullatif A , et al. Novel and recurrent mutations in the AIRE gene of autoimmune polyendocrinopathy syndrome type 1 (APS1) patients. Clin Genet 2009; 76 (5) 431-440
• 6 Millar S, Carson D. Clinical phenotypes of autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy seen in the Northern Ireland paediatric population over the last 30 years. Ulster Med J 2012; 81 (3) 118-122
• 7 Husebye ES, Perheentupa J, Rautemaa R, Kämpe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med 2009; 265 (5) 514-529
• 8 Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990; 322 (26) 1829-1836
• 9 Kluger N, Jokinen M, Krohn K, Ranki A. Gastrointestinal manifestations in APECED syndrome. J Clin Gastroenterol 2013; 47 (2) 112-120
• 10 Buber J, Goldenberg S, Eyal A, Mouallem M, Farfel Z. Hypocalcemia, prolonged QT interval and massive brain calcifications in an Iranian Jewish woman with APECED. Isr Med Assoc J 2008; 10 (12) 899-900
• 11 Adam A, Dixon AK. Grainger & Allison's Diagnostic Radiology. 5th ed. UK: Elsevier limited; 2009
• 12 Goel A, Bhatnagar MK, Vashishta A , et al. Hypoparathyroidism with extensive intracranial calcification: a case report. Postgrad Med J 1994; 70 (830) 913-915
• 13 Vassilatou E, Pikounis V, Economopoulos T, Hadjidakis D. Extensive bilateral cerebral calcifications in a patient with primary hypoparathyroidism. Arch Neurol 2010; 67 (7) 888-889
• 14 Scarpitta A, Pisciotta G, Fierro B. Basal ganglia calcifications and ALS syndrome. Ital J Neurol Sci 1994; 15 (5) 249-251
• 15 Jorens PG, Appel BJ, Hilte FA, Mahler C, De Deyn PP. Basal ganglia calcifications in postoperative hypoparathyroidism: a case with unusual characteristics. Acta Neurol Scand 1991; 83 (2) 137-140
• 16 Fujita T. Mechanism of intracerebral calcification in hypoparathyroidism [in Japanese]. Clin Calcium 2004; 14 (6) 55-57
• 17 Alfrey AC. The role of abnormal phosphorus metabolism in the progression of chronic kidney disease and metastatic calcification. Kidney Int Suppl 2004; 90 (90) S13-S17
• 18 Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S. Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol (Oxf) 2012; 77 (2) 200-206
• 19 Ryan S, McNicholas M, Eustace S. Anatomy for Diagnostic Imaging. 3rd ed. UK: Elsevier; 2011
• 20 Weissleder R, Wittenberg J, Harisinghani M , et al. Primer of Diagnostic Imaging. 5th ed. Missouri: Mosby; 2011
• 21 Kıroğlu Y, Callı C, Karabulut N, Oncel C. Intracranial calcifications on CT. Diagn Interv Radiol 2010; 16 (4) 263-269
• 22 Davies S. Chapman & Nakielny's Aids to Radiological Differential Diagnosis. 6th ed. UK: Elsevier Ltd; 2014
• 23 Livingston JH, Stivaros S, van der Knaap MS, Crow YJ. Recognizable phenotypes associated with intracranial calcification. Dev Med Child Neurol 2013; 55 (1) 46-57
• 24 Livingston J, Doherty D, Orcesi S , et al. COL4A1 mutations associated with a characteristic pattern of intracranial calcification. Neuropediatrics 2011; 42 (6) 227-233
• 25 Swami A, Kar G. Intracranial hemorrhage revealing pseudohypoparathyroidism as a cause of fahr syndrome. Case Rep Neurol Med 2011; 2011: 407567
• 26 Mamdani N, Repp AL, Seyoum B, Berhanu P. Idiopathic hypoparathyroidism presenting with severe hypocalcemia and asymptomatic basal ganglia calcification followed by acute intracerebral bleed. Endocr Pract 2007; 13 (5) 487-492