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
; 91(12): 4781-4785, 2006 Dec.
Article
en En
| MEDLINE
| ID: mdl-16968793
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 ANDMETHODS:
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 approximately 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).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Hiperplasia Suprarrenal Congénita
/
Genitales Masculinos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Límite:
Animals
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2006
Tipo del documento:
Article
País de afiliación:
Panamá