StAR Protein Deficiency in Clinical Practice - A Case Series From Saudi Arabia

Sep 29, 2026

Uploaded by Cipher

Steroidogenic acute regulatory (StAR) protein deficiency is a rare autosomal recessive disorder causing impaired steroid hormone biosynthesis, leading to congenital adrenal hyperplasia and variability in sexual development. Limited Saudi Arabian data prompted a retrospective case series describing clinical and genetic findings in seven genetically confirmed patients followed at a referral center. All patients had consanguineous ancestry and presented with a female external phenotype despite chromosomal sex, ranging from typical genitalia to feminization, electrolyte disturbances, and chronic salt-wasting, with rare cholestatic jaundice.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Introduction

Patients and Methods

Results

Conclusion

Wiley Case Reports in Endocrinology Volume 2026, Article ID 8489134, 7 pages [https://doi.org/10.1155/crie/8489134](https://doi.org/10.1155/crie/8489134) Case Series StAR Protein Deﬁciency in Clinical Practice: A Case Series From Saudi Arabia Abeer Alabduljabbar , 1 Dania Farooq ,2 Sara Abid ,2 Sara Aljazaeri ,2 Raghad Alhuthil , 1 and Afaf Alsagheir 1,2 1Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia 2College of Medicine, Alfaisal University, Riyadh, Saudi Arabia Correspondence should be addressed to Afaf Alsagheir; [asagheir@kfshrc.edu.sa](asagheir@kfshrc.edu.sa) Received 23 July 2025; Revised 6 December 2025; Accepted 17 December 2025 Academic Editor: Kalyani Sen Copyright © 2026 Abeer Alabduljabbar et al. Case Reports in Endocrinology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Objectives: Steroidogenic acute regulatory (StAR) protein deﬁciency is a rare autosomal recessive disorder that disrupts steroid hormone biosynthesis, resulting in congenital adrenal hyperplasia (CAH) and variations in sexual development. However, limited data is available in Saudi Arabia. Therefore, this study describes the clinical and genetic ﬁndings of seven Saudi patients with StAR deﬁciency. Methods: This case series was conducted at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi Arabia. Results: All seven patients were born to consanguineous parents, most commonly ﬁrst cousins. Five patients had a 46,XY karyotype, and two had a 46,XX karyotype. All were clinically diagnosed with CAH due to StAR deﬁciency. Despite their chromosomal sex, all presented with a female external phenotype. Clinical features ranged from typical female genitalia to varying degrees of feminization with bilateral inguinal gonads or undescended testes in 46,XY individuals. Most patients exhibited electrolyte disturbances and chronic salt-wasting. Interestingly, two cases presented with neonatal cholestatic jaundice. Genetic testing conﬁrmed homozygous pathogenic or likely pathogenic STAR variants in all cases. Dysmorphism occurred in one patient with (c.402T >G, p.Tyr134Ter) mutation. The ﬁve 46,XY patients underwent bilateral gonadectomy. All patients remain clinically stable on long-term steroid replacement. Conclusion: This study highlights the diverse clinical spectrum of StAR deﬁciency, ranging from early adrenal crisis to DSD and atypical presentations such as cholestasis. The ﬁndings underscore the importance of early genetic diagnosis and counseling, particularly in consanguineous populations, and point to the need for continued research into the clinical and molecular complexity of StAR deﬁciency. Keywords: 46,XY disorders of sex development; cholestasis; congenital adrenal hyperplasia; consanguinity; StAR deﬁciency; steroidogenesis 1. Introduction Steroid hormones are essential for maintaining homeostasis, supporting reproductive development, and regulating numerous physiological processes. Despite their varied functions, all steroid hormones originate from a common precursor, cholesterol. The steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis by facilitating the transport of cholesterol into the mitochondria, where it is converted topregnenolone, the rate-limiting step in steroid hormone biosynthesis [1] . Mutations in the STAR gene lead to a dysfunctional StAR protein, impairing cholesterol transport and disrupting steroid hormone production [2]. Clinically, this condition, known as StAR deﬁciency, presents as primary adrenal insufﬁciency and disorders of sex development (DSDs). Individuals with a 46,XY 2 Case Reports in Endocrinology karyotype may present with a phenotypically female appearance despite havin

FAQs

What is StAR protein deficiency and why is it clinically important?

StAR protein deficiency disrupts steroid hormone biosynthesis, causing congenital adrenal hyperplasia and disorders of sex development with variable presentation.

How were the seven patients in this case series diagnosed?

All seven patients were comprehensively evaluated and clinically diagnosed with CAH due to StAR deficiency, with genetic testing confirming homozygous pathogenic or likely pathogenic STAR variants.

What key clinical features did the patients show?

Despite chromosomal sex, all presented with a female external phenotype, with features ranging from typical genitalia to varying degrees of feminization; many had electrolyte disturbances and chronic salt-wasting, and two cases had neonatal cholestatic jaundice.

Sep 29, 2026

Uploaded by Cipher