title: Congenital lipoid adrenal hyperplasia (a rare form of adrenal insufficiency and ambiguous genitalia) caused by a novel mutation of the steroidogenic acute regulatory protein gene.
abstract: Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare autosomal recessive disorder of adrenal and gonadal steroidogenesis. It is most frequently caused by mutations in the steroidogenic acute regulatory protein (StAR) gene. Patients with lipoid CAH typically present with adrenal crisis in early infancy, and those with a 46,XY karyotype have female genitalia. However, it has been recently recognized that the phenotype can be quite variable, in that adrenal insufficiency is detected later in life and patients may have partially masculinized or even normal male genitalia. We report a patient assigned and reared as a female with a 46,XY karyotype and with a homozygous intron 2 (c.178+1G>C) splice site mutation of the StAR gene, which is a novel mutation that causes lipoid CAH. Her clinical presentation was somewhat atypical for a patient with classic lipoid CAH, marked by mild masculinization of the genitalia, detectable adrenal steroids at baseline, and ability to tolerate the stress of a surgical procedure with anesthesia without receiving glucocorticoid treatment.
  
  
  CONCLUSIONS
  There is significant phenotypic variability among patients with lipoid CAH. While splice site mutations in the StAR gene lead to premature translational termination, resulting in truncated and non-functional proteins, there is phenotypic variability among patients with such mutations. Our patient appears to have the more atypical phenotype compared to reported patients with similar mutations. The molecular mechanism underlying this heterogeneity remains unclear.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, Box 1198, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Oksana
authors.initials: O
authors.lastname: Lekarev
authors.forename: Delphine
authors.initials: D
authors.lastname: Mallet
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
mesh_terms: D000311:Adrenal Glands / Q000002:abnormalities*; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D058490:Disorder of Sex Development, 46,XY / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY; D006801:Humans; D007223:Infant; D059785:Karyotype; D008297:Male; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein
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