title: Family of two patients with congenital lipoid adrenal hyperplasia due to StAR mutation.
abstract: We are reporting the case of two sisters born to nonrelated French Canadian parents. Patient A is of female phenotype with 46,xy, and patient B with 46,xx. The children had severe manifestations of mineralocorticoid deficiency at the age of 11 and 4.5 months, respectively. Residual cortisol secretion seemed present until the age of 3 years for patient A and until 15 months in the case of her sister. Both patients responded to glucocorticoid and Florinef treatment. Patient A did not show any androgen secretion and gonadectomy was performed at the age of 13.4 years; estrogen therapy was started at the age of 14 years resulting in a good breast development and an increase of growth velocity. In patient B, a progressive development of secondary sex characters occurred at 11.6 years of age followed at 14 years by menarche associated with a normal secretion of LH, FSH and estradiol; regular menstruations continued up to her last visit at the age of 25 years. We identified a homozygous L275P mutation on the StAR gene of both patients and a heterozygous L275P mutation on that of their mother and father. In transfection analysis in COS-1 cells, the mutant L275P was well-expressed, but its StAR activity was 87% impaired. The remaining activity of the L275P StAR mutant is consistent with the moderate severity of clinical onset of manifestations.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Khoury
authors.forename: Lyne
authors.initials: L
authors.lastname: Ducharme
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: LeHoux
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007223:Infant; D007930:Leucine; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011392:Proline; D014162:Transfection; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011392:Proline; D007930:Leucine