Endocrine Abstracts

Background: Wolfram Syndrome (WS) is a rare autosomal recessive disorder characterised by early-onset diabetes and optic atrophy as well as a variable spectrum of other endocrine and neurological conditions. It is caused by mutations in the WFS1 gene. Previous reports have documented a variable prevalence of hypogonadism (6.3% of the international EURO-WABB registry, 34% of a German cohort); however the only UK cohort reported was of 10 males, 7 of whom had primary gonadal atrophy (Barrett et al 1996)

Aims: To review the prevalence of hypogonadism and pubertal disorders in a national cohort of children and young people (CYPD) attending the NHSE highly specialised multidisciplinary (MDT) service for paediatric WS.

Methods: Retrospective case review of all CYPD with WS seen in a single paediatric centre with documented WFS1 mutations since 2012. Electronic records were assessed for documented testicular volumes, age of menarche and menstrual irregularities as well as gonadotrophin, testosterone and oestrodiol levels

Results: 38 patients aged between 10-22 years (19M: 19F) were assessed. In males, of those who had completed puberty (n=15), 2 (13.3%) complained of erectile dysfunction, 3 (20%) had testicular volumes < 4mls aged 14 years and 3 (20%) required testosterone replacement therapy, 6 (40%) showed evidence of hypogonadism. In females, of those who had achieved menarche (n=18), 5 (27%) had evidence of irregular periods and 2 (11%) had menorrhagia requiring treatment. 1 (6%) had evidence of delayed puberty.

Discussion: In this contemporary UK cohort, the range of pubertal abnormalities in both males and females is significant with a high proportion of females reporting menstrual problems even with a normal puberty. This may cause particular issues in young women with multiple sensory deficits. The proportion of young male patients with hypogonadism and/or erectile dysfunction is also high and points to a wider phenotypic spectrum of gonadal abnormalities than previously suspected. 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.