Nonclassic Lipoid Congenital Adrenal Hyperplasia Masquerading as Familial Glucocorticoid Deficiency

• DOI: 10.1210/jc.2009-0467
• Publication Date: 2009-09-23T01:55:08Z
• Authors: Louise A. Metherell; Danielle Naville; George Halaby; Martine Begeot; Angela Huebner; Gudrun Nürnberg; Peter Nürnberg; Jane Green; Jeremy W. Tomlinson; Nils P. Krone; Lin Lin; Michael Racine; Dan M. Berney; John C. Achermann; Wiebke Arlt; Adrian J. L. Clark
• Keywords: Male; Genotype; DISORDERS; DNA Mutational Analysis; NR5A1; STEROIDOGENESIS; Polymorphism, Single Nucleotide; Diagnosis, Differential; TYPE-2; 03 medical and health sciences; 0302 clinical medicine; FEMALE-PATIENT; Humans; ADRENOCORTICOTROPIN RECEPTOR; Child; ACUTE-REGULATORY-PROTEIN; Adrenal Hyperplasia, Congenital; MUTATIONS; Infant; Pedigree; 3. Good health; Child, Preschool; STAR GENE; Mutation; Female; Adrenal Insufficiency

Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, likely succumb hypoglycemia and/or overwhelming infection. Mutations receptor (MC2R) and melanocortin 2 accessory protein (MRAP), FGD types 1 respectively, account for approximately 45% cases.A locus chromosome 8 has previously been linked disease three families, but no underlying gene defect date identified.The study design comprised single-nucleotide polymorphism genotyping mutation detection.The was conducted at secondary tertiary referral centers.Eighty probands families referred investigation genetic cause participated study.There were interventions.Analysis by array genotype one individual with revealed a large region homozygosity encompassing steroidogenic acute regulatory gene, STAR. We identified homozygous STAR mutations this patient his affected siblings. Screening our total cohort further nine four other families.Mutations usually lipoid congenital hyperplasia, characterized both gonadal steroid deficiency. Our results demonstrate that certain (R192C reported R188C) can present phenotype indistinguishable seen FGD.