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

## TL;DR

This study reports on seven Saudi patients with StAR protein deficiency, highlighting the condition's varied symptoms and the importance of genetic testing in consanguineous families.

## Contribution

The study provides new clinical and genetic data on StAR deficiency in Saudi Arabia, emphasizing its diverse presentation and the role of consanguinity.

## Key findings

- All seven patients had StAR deficiency confirmed by genetic testing with homozygous pathogenic variants.
- Clinical features included female external phenotype in 46,XY individuals and neonatal cholestatic jaundice in two cases.
- Bilateral gonadectomy was performed in five 46,XY patients, with long-term steroid replacement maintaining stability.

## Abstract

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.

This case series was conducted at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi Arabia.

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.

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.