Defining puberty and spectrum of hypogonadism in Alström Syndrome

Background: Alström syndrome (AS), has been extensively studied for its multi-system organ manifestations. Primary gonadal failure is well described in humans, but little is known about the intricacies of puberty and true incidence of hypogonadism within this population. Hypothesis: We aimed to define the onset and progression of puberty and the incidence of hypogonadism in male patients with AS. Methodology: A retrospective, observational cohort study was conducted on patients with AS across the UK and Italy national services. Additionally, the findings were correlated with Alms1 S701X mouse model as part of the current study. Results: We enrolled 28 paediatric patients (age 14.8 ±2.3) and 41 adult patients (age 34 ±12). All paediatric patients entered puberty at an appropriate age, but the highest testicular volume achieved by patients with AS was 9 ± 3ml in age group of 14-15-year-old boys. Among adults, 95% (39/41) had hypogonadism with primary gonadal failure. Testicular analysis of Alms1 S701X mouse model shows testicular atrophy with no evidence of fibrosis. Moreover, Alms1 S701X mice exhibit reduced sperm count and sperm motility compared to controls (29.03*106/ml vs 110.6*106/ml, 34.77% vs 70.18%). Conclusion: Our study sheds light on the reproductive aspects of AS across paediatric and adult populations with particular emphasis on testicular and pubertal development, and hypogonadism in adult life. Although, all the paediatric AS patients have age-appropriate onset of puberty, almost all exhibit hypogonadism with primary gonadal failure as adults. This mirrors the Alms1 S701X mouse model.