Gonadal Dysfunction in Wolfram Syndrome: A Prospective Study.

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Wolfram syndrome (WFS), a rare monogenic neurodegenerative disorder, is characterized by diabetes mellitus, optic atrophy, sensorineural hearing loss, and diabetes insipidus.
• Gonadal dysfunction, particularly hypogonadism, is an underrecognized but significant clinical feature of WFS, impacting patient quality of life.

Purpose of the Study:

• To prospectively assess the prevalence and characteristics of gonadal dysfunction in a cohort of genetically confirmed Wolfram syndrome patients.
• To evaluate hormonal profiles, reproductive parameters, and testicular/ovarian status in men and women with WFS.

Main Methods:

• Prospective follow-up of 45 WFS patients (25 men, 20 women) with genetically confirmed diagnosis.
• Men: hormonal evaluations, semen analysis, imaging, and testicular biopsies.
• Women: assessment of menstrual history, hormonal analyses (including AMH), and imaging.

Main Results:

• High prevalence of hypogonadism in men (76%), predominantly hypergonadotropic, with testicular damage observed on biopsies.
• Significant reproductive abnormalities in men, including azoospermia and altered semen parameters.
• Universal menstrual irregularities in women, with 20% experiencing premature menopause and evidence of early ovarian dysfunction.

Conclusions:

• Gonadal dysfunction is a prevalent and critical feature of Wolfram syndrome, necessitating systematic screening from puberty onwards.
• Comprehensive management addressing metabolic, psychological, and sexual health aspects is vital for improving WFS patients' long-term quality of life.
• Early detection and intervention for gonadal dysfunction can mitigate significant health challenges and support patients' aspirations for relationships and family.