title: Distinguishing deficiencies in the steroidogenic acute regulatory protein and the cholesterol side chain cleavage enzyme causing neonatal adrenal failure.
abstract: OBJECTIVE
  To determine the genetic basis of disordered steroidogenesis in Kuwaiti siblings.
  
  
  METHODS
  Two siblings (46,XX and 46,XY) had normal female external genitalia and severe glucocorticoid and mineralocorticoid deficiency presenting in the first month of life. Abdominal ultrasonography showed normal size adrenal glands, suggesting cholesterol side chain cleavage enzyme (P450scc) deficiency. The CYP11A1 gene encoding P450scc and the STAR gene encoding the steroidogenic acute regulatory protein (StAR) were directly sequenced from leukocyte DNA.
  
  
  RESULTS
  All exons and intron/exon boundaries of the CYP11A1 gene were normal; the STAR gene was homozygous for a novel 14-base deletion/frameshift in exon 4 (g.4643_4656del), so that no functional protein could be produced. Both parents and an unaffected sibling were heterozygous; zygosity was confirmed with a BsmF1 restriction fragment length polymorphism.
  
  
  CONCLUSIONS
  Unlike most patients with StAR deficiency, our patients did not have the massive adrenal hyperplasia typical of congenital lipoid adrenal hyperplasia. The distinction between StAR and P450scc deficiency may require gene sequencing.
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Zoran S
authors.initials: ZS
authors.lastname: Gucev
authors.forename: Meng Kian
authors.initials: MK
authors.lastname: Tee
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Diane K
authors.initials: DK
authors.lastname: Wherrett
authors.forename: Walter L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis / Q000235:genetics*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000172:deficiency* / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005091:Exons; D005192:Family Health; D005260:Female; D005938:Glucocorticoids / Q000172:deficiency; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D007730:Kuwait; D007962:Leukocytes / Q000378:metabolism; D008901:Mineralocorticoids / Q000172:deficiency; D008957:Models, Genetic; D009154:Mutation; D010375:Pedigree; D010750:Phosphoproteins / Q000172:deficiency*; D012150:Polymorphism, Restriction Fragment Length; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D005938:Glucocorticoids; D008901:Mineralocorticoids; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D004247:DNA; D002786:Cholesterol Side-Chain Cleavage Enzyme