This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baker, B. Y. Articles by Achermann, J. C. Search for Related Content PubMed PubMed Citation Articles by Baker, B. Y. Articles by Achermann, J. C. Related Collections Adrenal and Hypertension Pediatric Endocrinology

Nonclassic Congenital Lipoid Adrenal Hyperplasia: A New Disorder of the Steroidogenic Acute Regulatory Protein with Very Late Presentation and Normal Male Genitalia

Department of Pediatrics (B.Y.B., C.J.K., W.L.M.), University of California, San Francisco, California 94143; University College London Institute of Child Health and Department of Medicine (L.L., J.C.A.), University College London, London WC1N 1EH, United Kingdom; Endocrinology (J.R.), National Institute of Child Health, Karachi 75520, Pakistan; and Department of Pediatrics (C.P.S.), East Lancashire Hospitals National Health Service Trust, Blackburn BB2 3HH, United Kingdom

Address all correspondence and requests for reprints to: Dr. John C. Achermann, Biochemistry, Endocrinology, and Metabolism, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom. E-mail: j.achermann{at}ich.ucl.ac.uk; or to Professor Walter L. Miller, Department of Pediatrics, Box 0978, University of California, San Francisco, California 94143-0978. E-mail: wlmlab{at}ucsf.edu.

Context: Lipoid congenital adrenal hyperplasia is a severe disorder of adrenal and gonadal steroidogenesis caused by mutations in the steroidogenic acute regulatory protein (StAR). Affected children typically present with life-threatening adrenal insufficiency in early infancy due to a failure of glucocorticoid (cortisol) and mineralocorticoid (aldosterone) biosynthesis, and 46,XY genetic males have complete lack of androgenization and appear phenotypically female due to impaired testicular androgen secretion in utero.

Objective: The objective of this study was to investigate whether nonclassic forms of this condition exist.

Patients and Methods: Sequence analysis of the gene encoding StAR was undertaken in three children from two families who presented with primary adrenal insufficiency at 2–4 yr of age; the males had normal genital development. Identified mutants were tested in a series of biochemical assays.

Results: DNA sequencing identified homozygous StAR mutations Val187Met and Arg188Cys in these two families. Functional studies of StAR activity in cells and in vitro and cholesterol-binding assays showed these mutants retained 20% of wild-type activity.

Conclusions: These patients define a new disorder, nonclassic lipoid congenital adrenal hyperplasia, and represent a new cause of nonautoimmune Addison disease (primary adrenal failure).

This article has been cited by other articles:

				L. A. Metherell, D. Naville, G. Halaby, M. Begeot, A. Huebner, G. Nurnberg, P. Nurnberg, J. Green, J. W. Tomlinson, N. P. Krone, et al. Nonclassic Lipoid Congenital Adrenal Hyperplasia Masquerading as Familial Glucocorticoid Deficiency J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3865 - 3871. [Abstract] [Full Text] [PDF]

				P. Rubtsov, M. Karmanov, P. Sverdlova, P. Spirin, and A. Tiulpakov A Novel Homozygous Mutation in CYP11A1 Gene Is Associated with Late-Onset Adrenal Insufficiency and Hypospadias in a 46,XY Patient J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 936 - 939. [Abstract] [Full Text] [PDF]

				B. Ferraz-de-Souza, F. Martin, D. Mallet, R. E. Hudson-Davies, P. Cogram, L. Lin, D. Gerrelli, F. Beuschlein, Y. Morel, A. Huebner, et al. CBP/p300-Interacting Transactivator, with Glu/Asp-Rich C-Terminal Domain, 2, and Pre-B-Cell Leukemia Transcription Factor 1 in Human Adrenal Development and Disease J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 678 - 683. [Abstract] [Full Text] [PDF]

				C. J. Kim, L. Lin, N. Huang, C. A. Quigley, T. W. AvRuskin, J. C. Achermann, and W. L. Miller Severe Combined Adrenal and Gonadal Deficiency Caused by Novel Mutations in the Cholesterol Side Chain Cleavage Enzyme, P450scc J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 696 - 702. [Abstract] [Full Text] [PDF]

				D. Li, A. N. Urs, J. Allegood, A. Leon, A. H. Merrill Jr., and M. B. Sewer Cyclic AMP-Stimulated Interaction between Steroidogenic Factor 1 and Diacylglycerol Kinase {theta} Facilitates Induction of CYP17 Mol. Cell. Biol., October 1, 2007; 27(19): 6669 - 6685. [Abstract] [Full Text] [PDF]

				M. Abdulhadi-Atwan, A. Jean, W. K. Chung, K. Meir, Z. Ben Neriah, G. Stratigopoulos, S. E. Oberfield, I. Fennoy, H. J. Hirsch, A. Bhangoo, et al. Role of a Founder c.201_202delCT Mutation and New Phenotypic Features of Congenital Lipoid Adrenal Hyperplasia in Palestinians J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 4000 - 4008. [Abstract] [Full Text] [PDF]

				B. Y. Baker, R. F. Epand, R. M. Epand, and W. L. Miller Cholesterol Binding Does Not Predict Activity of the Steroidogenic Acute Regulatory Protein, StAR J. Biol. Chem., April 6, 2007; 282(14): 10223 - 10232. [Abstract] [Full Text] [PDF]