Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

J Electrocardiol. 2007 Nov-Dec;40(6):504-9. doi: 10.1016/j.jelectrocard.2006.12.013. Epub 2007 Feb 6.

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessively inherited disorder characterized by variable combinations of endocrine and nonendocrine symptoms. In this report, we describe two 20- and 17-year-old Turkish siblings presenting with typical symptoms of APECED, including Addison disease, alopecia, vitiligo, and hypopituitarism, in whom electrocardiographic examinations demonstrated an abnormal prolongation of the QT interval. In both cases, excessive hypocalcemia due to primary hypoparathyroidism was identified as the underlying cause of the long QT syndrome. Sequencing the gene coding for the autoimmune regulator revealed a homozygous missense mutation in exon 14 with a C-to-T transition that resulted in the substitution of proline 539 for leucine in the carboxy-terminal protein molecule. Our data show that a single point mutation in the transcriptional active autoimmune regulator protein is associated with inherited alterations in calcium metabolism resulting from autoimmune reactions against the parathyroid glands. This finding defines a congenital autoimmune disease as a hereditary long QT syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Electrocardiography / methods*
  • Female
  • Humans
  • Hypoparathyroidism / congenital*
  • Hypoparathyroidism / diagnosis*
  • Long QT Syndrome / congenital*
  • Long QT Syndrome / diagnosis*
  • Male
  • Pedigree
  • Polyendocrinopathies, Autoimmune / congenital*
  • Polyendocrinopathies, Autoimmune / diagnosis*