Novel StAR Gene Mutation Identified in a Moroccan Patient with Lipoid Congenital Adrenal Hyperplasia

Authors

  • Zaddouq Hanane Avicenne Hospital Center
  • Althel Pharel Opoko Endocrinology diabetology department, General Hospital of Loandjili, Pointe Noire, Republic of Congo
  • Khadija Belhassan Hassan II University Medical Center- Genetic Department- Fes Medical School
  • Intissar Haddiya Department of Nephrology , Faculty of medecine of Oujda , Morocco
  • Ahmed Gaouzi Endocrinology diabetology department, Rabat child Hospital , Morocco

DOI:

https://doi.org/10.30564/jer.v1i2.1149

Abstract

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive condition that results from the deficiency of one of the steroidogenesis enzymes responsible for cortisol biosynthesis. In the majority of cases, CAH is caused by 21-hydroxylase deficiency. More rarely, the deficiency concerns 11b-hydroxylase, 3b-hydroxysteroid dehydrogenase, 17hydroxylase, or exceptionally StAR and P450 oxydoreductase. Here, we report the case of a 3 year and 4 months old male child, born from a consanguineous marriage who presented at 15 months old with the salt-loss syndrome. Physical examination found generalized melanoderma, micropenis and bilateral cryptorchidism. Biological assessment at the time of diagnosis revealed hyponatremia, hyperkalemia, functional renal failure, hypoglycemia, low blood cortisol level, and high blood level of ACTH, suggesting primary adrenal insufficiency. The patient presented also with the abnormality of sexual differentiation with a 46 XY karyotype, testosteronemia level was low at the baseline and after HCG stimulation, pelvic ultrasound and Magnetic Raisonance Imaging (MRI) showed bilateral testicular atrophy in the inguinal position. The genetic study revealed a likely pathogenic homozygous variant in the StAR (steroidogenic acute regulatory) gene. Therapeutically, our patient was hydrated by saline solution and treated with hydrocortisone and fludrocortisone, then benefited from a surgical testicular correction marked by a favorable evolution. Although mutations in StAR gene are rare, they can be responsible for the defect in the early stage of steroidogenesis and therefore cause a deficiency in adrenal and sexual hormones biosynthesis.

Keywords:

StAR gene, Mutation, Congenital adrenal hyperplasia, Disorders of sex development

References

[1] Jasmeet Kaur , Luis Casas , and Himangshu S Bose. Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian patient. Endocrinology Diabetes &Metabolism Case Report, 2016. DOI: 10.1530/EDM-15-0119

[2] Walter L. Miller. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochimica et Biophysica Acta 1771, 2007: 663–676. DOI: 10.1016/j.bbalip.2007.02.012

[3] Bose, H.S., Lingappa, V.R. and Miller, W.L. Rapid regulation of steroidogenesis by mitochondrial protein import. Nature, 2002, 417: 87-91

[4] Carla Bizzarri1, Elisa Pisaneschi, Mafalda Mucciolo and al. Lipoid congenital adrenal hyperplasia by steroidogenic acute regulatory protein (STAR) gene mutation in an Italian infant:an uncommon cause of adrenal insufficiency, 2017. DOI: 10.1186/s13052-017-0371-y

[5] Bose HS. Mechanistic sequence of mitochondrial cholesterol transport by StAR proteins. Journal of Proteins and Proteomics, 2011, 2: 1–9.

[6] Miller WL & Bose HS. Early steps in steroidogenesis: intracellular cholesterol trafficking. Journal of Lipid Research, 2011, 52: 2111–2135. DOI: 10.1194/jlr.R016675

[7] 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. Journal of Clinical Endocrinology and Metabolism, 2000, 85: 3636–3639. DOI: 10.1210/jc.85.10.3636

[8] Bose HS, Pescovitz OH & Miller WL. Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein (StAR) gene. Journal of Clinical Endocrinology and Metabolism, 1997, 82: 1511–1515. DOI: 10.1210/jc.82.5.1511

[9] Fujieda K, Tajima T, Nakae J, Sageshima S, Tachibana K, Suwa S,Sugawara T & Strauss JF III. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene. Journal of Clinical Investigation, 1997, 99: 1265–1271.DOI: 10.1172/JCI119284

[10] Metherell LA, Naville D, Halaby G, Begeot M, Huebner A, Nu¨rnberg G,Nu¨rnberg P, Green J, Tomlinson JW, Krone KP et al. Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency. Journal of Clinical Endocrinology and Metabolism, 2009, 94: 3865–3871. DOI: 10.1210/jc.2009-0467

[11] Miller WL & Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrine Reviews, 2011, 32: 81–151.DOI: 10.1210/er.2010-0013

[12] Association SOS tuberculose et maladies respiratoires, 2012

[13] Bose HS, Sugawara T, Strauss JF 3rd, Miller WL. The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N Engl J Med. 1996, 335: 1870–8.

[14] Barbara J. Clark • Douglas M. Stocco. Cholesterol Transporters of the START Domain Protein Family in Health and Disease. Springer New York Heidelberg Dordrecht London, 2014. DOI: 10.1007/978-1-4939-1112-7

Downloads

How to Cite

Hanane, Z., Opoko, A. P., Belhassan, K., Haddiya, I., & Gaouzi, A. (2019). Novel StAR Gene Mutation Identified in a Moroccan Patient with Lipoid Congenital Adrenal Hyperplasia. Journal of Endocrinology Research, 1(2), 19–24. https://doi.org/10.30564/jer.v1i2.1149

Issue

Article Type

Articles

Downloads

Download data is not yet available.