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 Chen, X. Articles by Miller, W. L. Search for Related Content PubMed PubMed Citation Articles by Chen, X. Articles by Miller, W. L. Related Collections Adrenal and Hypertension

A Genetic Isolate of Congenital Lipoid Adrenal Hyperplasia with Atypical Clinical Findings

Department of Pediatrics and Metabolic Research Unit (X.C., B.Y.B., W.L.M.), University of California, San Francisco, California 94143-0978; and Pediatric Service Division, Saudi Aramco Hospital (M.A.A.), 31311 Dhahran, Saudi Arabia

Address all correspondence and requests for reprints to: Prof. Walter L. Miller, Department of Pediatrics, Building MR-IV, Room 205, University of California, San Francisco, California 94143-0978. E-mail: wlmlab{at}itsa.ucsf.edu.

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH, eventually destroying all adrenal and gonadal steroidogenesis. Lipoid CAH is caused by mutations in the steroidogenic acute regulatory protein (StAR), which facilitates the entry of cholesterol into mitochondria to initiate steroidogenesis. Patients with lipoid CAH typically present with a salt-losing crisis in the first 2 months of life, although presentation as late as 10 months with partial retention of StAR activity has been reported. We describe eight patients from six Saudi Arabian families who were first diagnosed at 1–14 months of age (median, 4–7 months; mean, 7 months). Five patients were 46,XY, and three were 46,XX. At presentation, all had hyponatremia, hyperkalemia, elevated ACTH, and low cortisol. Pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate were all low in those patients in whom it was measured. DNA sequencing showed that one patient was homozygous for the StAR mutation M144R, and the other seven, from five apparently unrelated families, were homozygous for the StAR mutation R182H. Each mutation was recreated in a human StAR cDNA expression vector and found to be wholly inactive in a standard assay of COS-1 cells cotransfected with the cholesterol side-chain cleavage enzyme system. Thus, the loss of all assayable activity in vitro correlated poorly with the later onset of clinical symptoms in these patients. Lipoid CAH may present much later in life than previously thought.

This article has been cited by other articles:

				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]

				B. Y. Baker, L. Lin, C. J. Kim, J. Raza, C. P. Smith, W. L. Miller, and J. C. Achermann Nonclassic Congenital Lipoid Adrenal Hyperplasia: A New Disorder of the Steroidogenic Acute Regulatory Protein with Very Late Presentation and Normal Male Genitalia J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4781 - 4785. [Abstract] [Full Text] [PDF]

				B. Y. Baker, D. C. Yaworsky, and W. L. Miller A pH-dependent Molten Globule Transition Is Required for Activity of the Steroidogenic Acute Regulatory Protein, StAR J. Biol. Chem., December 16, 2005; 280(50): 41753 - 41760. [Abstract] [Full Text] [PDF]

				A. Bhangoo, W.-X. Gu, S. Pavlakis, H. Anhalt, L. Heier, S. Ten, and J. L. Jameson Phenotypic Features Associated with Mutations in Steroidogenic Acute Regulatory Protein J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6303 - 6309. [Abstract] [Full Text] [PDF]

				C. E. Fluck, A. Maret, D. Mallet, S. Portrat-Doyen, J. C. Achermann, B. Leheup, G. E. Theintz, P. E. Mullis, and Y. Morel A Novel Mutation L260P of the Steroidogenic Acute Regulatory Protein Gene in Three Unrelated Patients of Swiss Ancestry with Congenital Lipoid Adrenal Hyperplasia J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5304 - 5308. [Abstract] [Full Text] [PDF]