Bowel dysfunction is a common problem in patients with metabolic/neurological disorders and ranges from constipation and intestinal pseudo-obstruction to intractable fecal incontinence. However, the mechanism of it remains not entirely clear, although the bowel dysfunction severely affects the quality of life in the patients.
Here, we report on a 32-year-old man with clinically diagnosed Wolfram syndrome (WFS), which is thought to be caused by a WFS1 gene mutation that encodes wolframin, an endoplasmic reticulum calcium channel in neurons and pancreatic β-cells. He also presented with severe bowel (urgent fecal incontinence that started at age 24 years) and bladder dysfunction. His previous illnesses included congenital cataracts, progressive optic atrophy that started at age 3 years, and diabetes that started at age 11 years (under insulin treatment). At that time, he had first begun to have mild urinary urgency/frequency. At age 21 years, he was found to have hearing loss and diabetes insipidus (then, urine output 1,200 ml/day under desmopressin treatment with no upper urinary tract dilatation). A nerve conduction study in the extremities revealed sensory-dominant axonal neuropathy. A brain magnetic resonance imaging scan revealed atrophy in the cerebellum and the brainstem, although he had no cerebellar ataxia. Urodynamic study with pressure-flow analysis showed detrusor filling overactivity/voiding underactivity without detrusor-sphincter dyssynergia. Twenty milligrams a day of propiverine, an anticholinergic agent, once ameliorated his bladder and bowel symptoms. However, he again became fecally incontinent, and after tapering the drug, we performed a bowel function test in the patient. Colonic transit time test using Sitzmarks (1) showed normal colonic transit time (24.0 h, 16.0 < normal < 48.0). However, videomanometry (1) showed loss of spontaneous phasic rectal contractions (SPRCs) that were seen in normal subjects and sphincter weakness. Then he was taught to perform pelvic floor exercise, and his fecal incontinence became slightly ameliorated.
Bladder dysfunctions reported in WFS include hydroureter due to excessive urine output (2), detrusor-sphincter dyssynergia (2), and detrusor overactivity (2); the latter was the main bladder abnormality in our patient, presumably reflecting the brainstem atrophy. Previously, bowel dysfunction has only rarely been documented in WFS (3, 4). In our case, loss of SPRCs and sphincter weakness were the main bowel abnormalities. The SPRCs are likely to reflect the intrinsic neuronal activities of the pacemaker cells in the myenteric plexus, which can be damaged in peripheral neuropathies that involve small fibers. Sphincter tone is maintained by the extrinsic somatic nerve for the external sphincter and sympathetic nerve for the internal sphincter, respectively, which can also be damaged in peripheral neuropathies. These bowel dysfunctions need specific management to maximize the quality of life in patients with WFS.
