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Bo Y. Baker, Lin Lin, Chan J. Kim, Jamal Raza, Claire P. Smith, Walter L. Miller, John C. Achermann, Nonclassic Congenital Lipoid Adrenal Hyperplasia: A New Disorder of the Steroidogenic Acute Regulatory Protein with Very Late Presentation and Normal Male Genitalia, The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 12, 1 December 2006, Pages 4781–4785, https://doi.org/10.1210/jc.2006-1565
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Abstract
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).
