Distinguishing Deficiencies in the Steroidogenic Acute Regulatory Protein and the Cholesterol Side Chain Cleavage Enzyme Causing Neonatal Adrenal Failure

• Published in: The Journal of pediatrics 2013-04, Vol.162 (4), p.819-822
• Main Authors: Gucev, Zoran S., MD, Tee, Meng Kian, PhD, Chitayat, David, MD, Wherrett, Diane K., MD, Miller, Walter L., MD
• Format: Article
• Language: English
• Subjects: adrenal glands; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - genetics; cholesterol; Cholesterol Side-Chain Cleavage Enzyme - deficiency; Cholesterol Side-Chain Cleavage Enzyme - genetics; DNA; DNA - metabolism; Exons; Family Health; Female; genes; genitalia; Glucocorticoids - deficiency; heterozygosity; homozygosity; Homozygote; Humans; hyperplasia; Infant, Newborn; Introns; Kuwait; Leukocytes - metabolism; Mineralocorticoids - deficiency; Models, Genetic; Mutation; parents; patients; Pediatrics; Pedigree; Phosphoproteins - deficiency; Polymorphism, Restriction Fragment Length; restriction fragment length polymorphism; siblings; steroidogenesis; ultrasonography
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2012.10.012

Objectives To determine the genetic basis of disordered steroidogenesis in Kuwaiti siblings. Study design Two siblings (46,XX and 46,XY) had normal female external genitalia and severe glucocorticoid and mineralocorticoid deficiency presenting in the first month of life. Abdominal ultrasonography showed normal size adrenal glands, suggesting cholesterol side chain cleavage enzyme (P450scc) deficiency. The CYP11A1 gene encoding P450scc and the STAR gene encoding the steroidogenic acute regulatory protein (StAR) were directly sequenced from leukocyte DNA. Results All exons and intron/exon boundaries of the CYP11A1 gene were normal; the STAR gene was homozygous for a novel 14-base deletion/frameshift in exon 4 (g.4643_4656del), so that no functional protein could be produced. Both parents and an unaffected sibling were heterozygous; zygosity was confirmed with a BsmF1 restriction fragment length polymorphism. Conclusions Unlike most patients with StAR deficiency, our patients did not have the massive adrenal hyperplasia typical of congenital lipoid adrenal hyperplasia. The distinction between StAR and P450scc deficiency may require gene sequencing.