Splenic structural and functional abnormalities in individuals with NR5A1/SF-1 variants

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Pediatric Endocrinology

Background:

• Steroidogenic factor 1 (SF-1), encoded by NR5A1, plays a critical role in spleen development and function.
• Variants in the NR5A1 gene are associated with abnormal spleen development, leading to hyposplenism.
• Hyposplenism increases susceptibility to severe infections and complications.

Purpose of the Study:

• To determine the prevalence of hyposplenism in French patients with NR5A1 variants.
• To characterize the principal features of hyposplenism in this cohort.
• To investigate the relationship between NR5A1 variants and splenic anomalies.

Main Methods:

• A cross-sectional, multicenter study was conducted on 34 patients with heterozygous NR5A1 variants.
• Participants underwent splenic imaging (ultrasound, CT, or MRI).
• Pocked red blood cell (pRBC) quantification was used to assess splenic function: <7% (normal), 7-20% (moderate hyposplenism), >20% (severe hyposplenism).

Main Results:

• Functional hyposplenism was observed in 61.7% of patients (21/34), with 47% (16/34) having severe forms.
• Morphological spleen abnormalities were present in 44.1% (15/34), including asplenia in 11.7% (4/34).
• All patients with morphological abnormalities had functional hyposplenism, but 28% with functional hyposplenism had normal spleen morphology.

Conclusions:

• Functional hyposplenism is frequent in patients with NR5A1 variants, irrespective of genotype or gonadal phenotype.
• Assessing splenic function is essential for patient management.
• Preventive measures are critical for patients diagnosed with hyposplenism.