ESPE Abstracts

Background: Wolfram Syndrome (WS) is a rare progressive neurodegenerative disorder characterised by early-onset diabetes and optic atrophy as well as a variable spectrum of other clinical features. It is caused by mutations in the WFS1 gene. There is currently limited published literature on pubertal progression and gonadal function in WS.

Aims: To review the gonadal function and pubertal progression of a cohort of adolescent and young adult patients seen within a single national service for Wolfram Syndrome

Methods: Retrospective case review of all CYPD with WS who had completed puberty, seen in a single paediatric centre with classical WS mutations. Electronic records were assessed for documented testicular volumes, age of menarche and menstrual irregularities as well as gonadotrophin, testosterone and oestrodiol levels.

Results: 25 patients (16-23 years) were assessed (12M: 13F). In males, there was evidence of hypogonadism in 5 (41.7%) with both hypogonadotrophic and hypergonadatrophic hypogonadism seen (n=2 and n= 3 respectively). All 5 patients had evidence of low Inhibin B levels. In males with normal testosterone and gonadatrophin levels (n=7), no evidence of low inhibin B was seen. In addition, 3 (25%) male patients had erectile dysfunction (ED) documented (not associated with hypogonadism but all had bladder dysfunction). 3 (25%) required testosterone replacement to complete puberty. In females, 1 (7.6%) showed evidence of hypogonadotrophic hypogonadism with primary amenorrhoea. There was evidence of menstrual irregularities in 53.8% (n=7). Bladder dysfunction was common in both males and females with > 75% (9M and 10F).

Conclusions: In this contemporary young adult UK cohort we demonstrate a significant number of pubertal abnormalities in both males and females. Over half of females reported menstrual irregularities despite a normal puberty. This may cause particular issues in young women with sensory deficits. In young men, almost half showed evidence of hypogonadism on completion of puberty with a smaller number needing testosterone replacement into adulthood. The proportion of young males with ED is also high although may be related to both diabetes and bladder dysfunction requiring intermittent catheterization. We show that there is a wider phenotypic spectrum of gonadal abnormalities as well as a very high proportion of bladder dysfunction in young adulthood than previously suspected in WS. Young people with Wolfram syndrome should have a full pubertal assessment and that of gonadal function as a baseline, with hormone replacement and psychosexual counselling as necessary.