title: Primary Adrenocortical Insufficiency Case Series: Genetic Etiologies More Common than Expected.
abstract: OBJECTIVE
  Primary adrenal insufficiency (AI) is an important cause of morbidity in children. Our objectives were: (1) to describe the clinical presentation of children with new-onset primary AI, and (2) to identify monogenic causes of primary AI in children.
  
  
  METHODS
  Chart review and mutation detection in candidate genes were conducted for 11 patients with primary AI.
  
  
  RESULTS
  The likely cause of AI was determined in 9 patients. One had a homozygous MC2R mutation associated with familial glucocorticoid deficiency. Two had the same homozygous mutation in the AIRE gene which is associated with type 1 autoimmune polyglandular syndrome. One patient had a heterozygous change in this gene of undetermined significance. Five were homozygous for the previously reported p.R188C STAR mutation causing nonclassic lipoid congenital adrenal hyperplasia, representing the largest cohort of such patients from a single geographic area. In the remaining 2 patients, no clear etiology was identified.
  
  
  CONCLUSIONS
  We recommend genetic testing for patients who have negative anti-adrenal antibodies or suggestive family history. Diagnosing a genetic etiology can provide information about prognosis and treatment, and is therefore beneficial for patients. Our high proportion of patients with nonclassic lipoid congenital adrenal hyperplasia likely represents a founder effect.
authors.affiliation: Discipline of Pediatrics (Division of Endocrinology), Memorial University of Newfoundland, St. John's, Nfld., Canada.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tsai
authors.forename: Jane
authors.initials: J
authors.lastname: Green
authors.forename: Lou A
authors.initials: LA
authors.lastname: Metherell
authors.forename: Fiona
authors.initials: F
authors.lastname: Curtis
authors.forename: Bridget
authors.initials: B
authors.lastname: Fernandez
authors.forename: Ara
authors.initials: A
authors.lastname: Healey
authors.forename: Joseph
authors.initials: J
authors.lastname: Curtis
mesh_terms: D000224:Addison Disease / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D044103:Receptor, Melanocortin, Type 2; D014157:Transcription Factors; D000096927:AIRE Protein; D000098682:Steroidogenic Acute Regulatory Protein