Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian patient. (1st March 2016)

• Record Type: Journal Article
• Authors: Kaur, Jasmeet; Casas, Luis; Bose, Himangshu S
• Is Part Of: Endocrinology, diabetes & metabolism case reports. (2016)
• Publication Date: 2016-03-01
• Subjects: Paediatric -- Female -- Other -- United States; Adrenal -- Adrenal -- Pregnenolone -- Hydroxypregnenolone -- Cortisol -- Renin -- ACTH -- Progesterone -- Congenital adrenal hyperplasia -- Adrenal salt-wasting crisis; Salt wasting -- Hyperpigmentation -- Dehydration -- Pregnenolone -- Hydroxypregnenolone -- Molecular genetic analysis -- Protein folding analysis* -- Cortisol -- ACTH -- Renin (blood) -- Potassium -- DNA sequencing -- Ultrasound scan -- Sodium -- Liquid chromatography-mass spectrometry -- Protein fingerprinting -- Progesterone -- Chromatography -- Western blotting -- Gonadectomy -- Glucocorticoids -- Fludrocortisone -- Mineralocorticoids -- Hydrocortisone; Insight into disease pathogenesis or mechanism of therapy -- March -- 2016; Endocrinology -- Periodicals; Diabetes -- Periodicals; Diabetes Mellitus; Endocrinology; Diabetes; Endocrinology; Case Reports; Periodicals; Periodicals; 616.4
• DOI: 10.1530/EDM-15-0119
• Languages: English
• ISSNs: 2052-0573

Abstract

Summary: Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR . Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions. Learning points: STAR mutations cause lipoid CAH. This is a pure population from a caucasian family. Mutation ablated STAR activity. The mutation resulted in loosely folded conformation of STAR.