Bladder dysfunction in Wolfram syndrome is highly prevalent and progresses to megacystis

Area of Science:

• Genetics and rare diseases
• Urology and nephrology
• Endocrinology

Background:

• Wolfram syndrome is a rare genetic disorder typically characterized by diabetes mellitus and insipidus, sensorineural deafness, and optic atrophy.
• Bladder dysfunction is not a classically recognized symptom of Wolfram syndrome, but has been observed frequently in clinical practice.

Purpose of the Study:

• To quantify the prevalence and characteristics of bladder dysfunction in patients with Wolfram syndrome.
• To investigate the association between bladder behavior, symptoms, and genotype in this cohort.

Main Methods:

• A national cohort study analyzed data from 40 Wolfram syndrome patients managed by a multidisciplinary team.
• Non-invasive urodynamics (NIU) assessed bladder capacity, voided volume, post-void residual, and uroflow patterns.
• Bladder function was categorized as normal, overactive (OAB), or underactive (UAB), and correlated with symptoms and genotype.

Main Results:

• Of 38 patients who underwent NIU, 25 (66%) exhibited underactive bladder (UAB), 9 (24%) overactive bladder (OAB), and 4 (11%) normal bladder function.
• Bladder dysfunction patterns significantly correlated with reduced predicted bladder capacity and impaired bladder emptying.
• While symptoms were reported in only 30% of children, progression to megacystis was observed with age.

Conclusions:

• Bladder dysfunction is highly prevalent in Wolfram syndrome, with underactive bladder being the most common form.
• Despite a high prevalence, many children are asymptomatic, but the progression towards megacystis suggests a neuropathic myogenic failure requiring future management.
• Early identification and monitoring of bladder function are crucial for managing Wolfram syndrome patients.