Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene.
Open Access
- 15 March 1997
- journal article
- case report
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 99 (6) , 1265-1271
- https://doi.org/10.1172/jci119284
Abstract
Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. We report here the clinical, endocrinological, and molecular analyses of two unrelated Japanese kindreds of 46,XX subjects affected with lipoid CAH who manifested spontaneous puberty. Phenotypic female infants with 46,XX karyotypes were diagnosed with lipoid CAH as newborns based on a clinical history of failure to thrive, hyperpigmentation, hyponatremia, hyperkalemia, and low basal values of serum cortisol and urinary 17-hydroxycorticosteroid and 17-ketosteroid. These patients responded to treatment with glucocorticoid and 9alpha-fludrocortisone. Spontaneous thelarche occurred in association with increased serum estradiol levels at the age of 10 and 11 yr, respectively. Pubic hair developed at the age of 12 yr 11 mo in one subject and menarche was at the age of 12 yr in both cases. Both subjects reported periodic menstrual bleeding and subsequently developed polycystic ovaries. To investigate the molecular basis of the steroidogenic lesion in these patients, the StAR gene was characterized by PCR and direct DNA sequence analyses. DNA sequence analysis revealed that one patient is homozygous for the Gln 258 Stop mutation in exon 7 and that the other patient is a compound heterozygote with the Gln 258 Stop mutation and a single A deletion at codon 238 in the other allele causing a frame-shift, which renders the StAR protein nonfunctional. These findings demonstrate that ovarian steroidogenesis can be spared to some extent through puberty when the StAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis which are characteristics of this disease.Keywords
This publication has 11 references indexed in Scilit:
- Regulation of the Acute Production of Steroids in Steroidogenic Cells*Endocrine Reviews, 1996
- T→A transversion 11 bp from a splice acceptor site in the human gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasiaHuman Molecular Genetics, 1995
- Structure of the human steroidogenic acute regulatory (StAR) protein gene: StAR stimulates mitochondrial cholesterol 27-hydroxylaseBiochemistry, 1995
- Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.Proceedings of the National Academy of Sciences, 1995
- No mutation in cytochrome P450 side chain cleavage in a patient with congenital lipoid adrenal hyperplasia.Journal of Clinical Endocrinology & Metabolism, 1994
- The human peripheral renzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasiaGenomics, 1993
- Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia.Journal of Clinical Investigation, 1991
- Molecular Biology of Steroid Hormone Synthesis*Endocrine Reviews, 1988
- Cholesterol side-chain cleavage enzyme activity and cytochrome P-450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease)Clinica Chimica Acta; International Journal of Clinical Chemistry, 1977
- EVIDENCE FOR DEFICIENT 20α-CHOLESTEROL-HYDROXYLASE ACTIVITY IN ADRENAL TISSUE OF A PATIENT WITH LIPOID ADRENAL HYPERPLASIAActa Endocrinologica, 1972