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

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 sh...

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Bibliographic Details
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
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Summary: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.
ISSN:0022-3476
1097-6833
DOI:10.1016/j.jpeds.2012.10.012