Progressive generalized lipodystrophy as a manifestation of autoimmune polyglandular syndrome type 1

Abstract

Context: The classic clinical triad of autoimmune polyglandular syndrome type 1 (APS1) is composed of Addison disease, hypoparathyroidism, and chronic mucocutaneous candidiasis; however, other endocrine and nonendocrine features of APS1 may occur. Here we report on a challenging diagnosis of APS1 in a patient who was first referred to a physician at the age of 15 months with a progressive generalized lipodystrophy, 2 years before the onset of oral candidiasis and autoimmune hepatitis, and 3 years before the manifestation of adrenal insufficiency. Case Description: We describe a boy who has been suffering from progressive weight loss and sc fat disappearance, most evident on the limbs, since the age of 15 months. Sequencing of various lipodystrophy candidate genes showed no mutations. At the age of 4 years, autoimmune hepatitis (with rapid progression to hepatic cirrhosis Child-Pugh class C) and oral candidiasis were diagnosed consequently, and 1 year later the patient showed symptoms of adrenal crisis. APS1 was confirmed by detecting a homozygous c.769C>T p.R257X mutation in AIRE gene. Conclusions: Acquired lipodystrophy is known to be associated with autoimmune disorders. To our knowledge, however, this is the first time that acquired generalized lipodystrophy has been identified in association with APS1.