Yonsei Med J.  2011 Nov;52(6):1035-1038. 10.3349/ymj.2011.52.6.1035.

Prenatal Diagnosis of Congenital Lipoid Adrenal Hyperplasia (CLAH) by Molecular Genetic Testing in Korean Siblings

• Ko HS
• Lee S
• Chae H
• Choi SK
• Kim M
• Park IY
• Suh BK
• Shin JC

• KMID: 1058829
• DOI: http://doi.org/10.3349/ymj.2011.52.6.1035

Abstract

Congenital lipoid adrenal hyperplasia (CLAH) is caused by mutations to the steroidogenic acute regulatory protein (StAR) gene associated with the inability to synthesize all adrenal and gonadal steroids. Inadequate treatment in an infant with this condition may result in sudden death from an adrenal crisis. We report a case in which CLAH developed in Korean siblings; the second child was prenatally diagnosed because the first child was affected and low maternal serum estriol was detected in a prenatal screening test. To our knowledge, this is the first prenatal diagnosis of the Q258X StAR mutation, which is the only consistent genetic cluster identified to date in Japanese and Korean populations.

Keyword

Lipoid hyperplasia; congenital; prenatal; sibling

MeSH Terms

46, XY Disorders of Sex Development/*diagnosis/*genetics
Adrenal Hyperplasia, Congenital/*diagnosis/*genetics
Adult
Asian Continental Ancestry Group
Female
Genetic Testing/*methods
Humans
Korea
Prenatal Diagnosis/*methods

Figure

• 

  Fig. 1 StAR sequencing chromatogram (A: control sample, B: fetus). C to T substitution is expected to produce a glycine to stop codon substitution.

Reference

1. Miller WL. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochim Biophys Acta. 2007. 1771:663–676.

2. Jean A, Mansukhani M, Oberfield SE, Fennoy I, Nakamoto J, Atwan M, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia (CLAH) by estriol amniotic fluid analysis and molecular genetic testing. Prenat Diagn. 2008. 28:11–14.

3. Lin D, Sugawara T, Strauss JF 3rd, Clark BJ, Stocco DM, Saenger P, et al. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science. 1995. 267:1828–1831.

4. Bose HS, Sato S, Aisenberg J, Shalev SA, Matsuo N, Miller WL. Mutations in the steroidogenic acute regulatory protein (StAR) in six patients with congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab. 2000. 85:3636–3639.

5. Nakae J, Tajima T, Sugawara T, Arakane F, Hanaki K, Hotsubo T, et al. Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasia. Hum Mol Genet. 1997. 6:571–576.

6. Yoo HW, Kim GH. Molecular and clinical characterization of Korean patients with congenital lipoid adrenal hyperplasia. J Pediatr Endocrinol Metab. 1998. 11:707–711.

7. Bose HS, Sugawara T, Strauss JF 3rd, Miller WL. International Congenital Lipoid Adrenal Hyperplasia Consortium. The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N Engl J Med. 1996. 335:1870–1878.

8. Canick JA, MacRae AR. Second trimester serum markers. Semin Perinatol. 2005. 29:203–208.

9. Palomaki GE, Bradley LA, Knight GJ, Craig WY, Haddow JE. Assigning risk for Smith-Lemli-Opitz syndrome as part of 2nd trimester screening for Down's syndrome. J Med Screen. 2002. 9:43–44.

10. Bartels I, Caesar J, Sancken U. Prenatal detection of X-linked ichthyosis by maternal serum screening for Down syndrome. Prenat Diagn. 1994. 14:227–229.

11. Opitz JM, Gilbert-Barness E, Ackerman J, Lowichik A. Cholesterol and development: the RSH ("Smith-Lemli-Opitz") syndrome and related conditions. Pediatr Pathol Mol Med. 2002. 21:153–181.

12. Grumbach MM, Auchus RJ. Estrogen: consequences and implications of human mutations in synthesis and action. J Clin Endocrinol Metab. 1999. 84:4677–4694.

13. Auchus RJ. The genetics, pathophysiology, and management of human deficiencies of P450c17. Endocrinol Metab Clin North Am. 2001. 30:101–119. vii

14. Saenger P, Klonari Z, Black SM, Compagnone N, Mellon SH, Fleischer A, et al. Prenatal diagnosis of congenital lipoid adrenal hyperplasia. J Clin Endocrinol Metab. 1995. 80:200–205.

15. Marshall I, Ugrasbul F, Manginello F, Wajnrajch MP, Shackleton CH, New MI, et al. Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen. J Clin Endocrinol Metab. 2003. 88:4144–4148.

16. Hensleigh PA, Moore WV, Wilson K, Tulchinsky D. Congenital X-linked adrenal hypoplasia. Obstet Gynecol. 1978. 52:228–232.

17. Reutens AT, Achermann JC, Ito M, Ito M, Gu WX, Habiby RL, et al. Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita. J Clin Endocrinol Metab. 1999. 84:504–511.