title: Hypoparathyroidism and central diabetes insipidus: in search of the link.
abstract: Two siblings (a 15-year-old boy and an 11-year-old girl) who presented with hypocalcemic seizure at the age of 2 years and 2 months (boy) and 2 years and 4 months (girl) were diagnosed with hypoparathyroidism. At the age of 3 years, the girl developed central diabetes insipidus with good response to desmopressin acetate treatment. The family history was unremarkable, and there was no consanguinity between the parents. The father is of Iraqi/Egyptian Jewish origin and the mother is of Iranian/Romanian Jewish origin. Sequence analysis of the candidate genes for isolated hypoparathyroidism encoding calcium-sensing receptor, parathyroid hormone, and glial cells missing homolog B did not reveal any mutations. Whole-exome sequencing identified a homozygous mutation in the autoimmune regulatory gene (AIRE), c.374A>G;p.Y85C, characteristic for Jewish Iranians with autoimmune polyendocrine syndrome type 1 (APS1), which was confirmed by the Sanger sequencing. Antibodies against the adrenal, pancreatic islet cell, ovary, thyroid, pituitary, celiac, and parietal cell were negative in both siblings, while anti-diuretic hormone antibodies were positive only in the girl. No other symptoms or signs of APS1 developed during all the years of follow-up.
  
  
  CONCLUSIONS
  APS1 should be part of the differential diagnosis in children presenting with isolated hypoparathyroidism or hypoparathyroidism with central diabetes insipidus (CDI). These cases show that the AIRE mutation characteristic of Iranian Jews can also be found in non-Iranian Jews.
authors.affiliation: Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann St., 6423906, Tel Aviv, Israel, ori.eyal27@gmail.com.
authors.forename: Ori
authors.initials: O
authors.lastname: Eyal
authors.forename: Asaf
authors.initials: A
authors.lastname: Oren
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Michael
authors.initials: M
authors.lastname: Mannstadt
authors.forename: Auryan
authors.initials: A
authors.lastname: Szalat
authors.forename: Margalit
authors.initials: M
authors.lastname: Bleiberg
authors.forename: Yosef
authors.initials: Y
authors.lastname: Weisman
authors.forename: Naomi
authors.initials: N
authors.lastname: Weintrob
mesh_terms: D000293:Adolescent; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D020790:Diabetes Insipidus, Neurogenic / Q000097:blood / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007011:Hypoparathyroidism / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation; D010281:Parathyroid Hormone / Q000097:blood; D010375:Pedigree; D035781:Siblings; D014157:Transcription Factors / Q000097:blood / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D004247:DNA; D010281:Parathyroid Hormone; D014157:Transcription Factors; D000096927:AIRE Protein