Taste and smell function in Wolfram syndrome

Abstract

Background: Wolfram syndrome is a rare genetic disease characterized by insulin-dependent diabetes, optic nerve atrophy, sensorineural hearing loss and neurodegeneration. Although olfactory dysfunction, a classical clinical marker of neurodegenerative processes, has been reported in Wolfram syndrome, its use as a clinical marker in Wolfram is limited due to data scarcity. In addition, it is unknown whether Wolfram syndrome affects the sense of taste. Methods: Smell and taste perception were assessed in participants with Wolfram syndrome (n = 40) who were 15.1 ± 6.0 years of age (range: 5.1-28.7 years) and two sex-and age-matched control groups: one group with type 1 diabetes mellitus (T1D; n = 25) and a healthy control group (HC; n = 29). Smell sensitivity was assessed by measuring n-butanol detection thresholds and smell identification by using the University of Pennsylvania Smell Identification Test (UPSIT). Taste function was assessed using NIH Toolbox, which includes the assessment of sucrose (sweet) taste preference, and perceived intensity of sucrose, sodium chloride (salty), and quinine hydrochloride (bitter) both in the tip of the tongue (regional test) and the whole mouth. Results: Smell sensitivity was not significantly different among groups; however, smell identification was impaired in Wolfram syndrome, as reflected by significantly lower UPSIT scores in Wolfram syndrome compared to HC and T1D (P < 0.001). Compared to participants in the control groups, participants with Wolfram syndrome had a blunted perception of sweetness and saltiness when taste stimuli were applied regionally (P < 0.05), but differences in perceived intensity were no longer significant among groups when taste stimuli were tasted with the whole mouth. Groups preferred similar sucrose concentrations. Conclusion: Wolfram syndrome was associated with olfactory dysfunction. However, the olfactory dysfunction was qualitative (related to smell identification) and not secondary to olfactory insensitivity or diabetes, suggesting is arising from dysfunction in central olfactory brain regions. In contrast to olfaction, and despite decreased perception of taste intensity in the anterior tongue, the sense of taste was overall well-conserved in individuals with Wolfram syndrome. Future longitudinal studies of taste and smell perception in Wolfram syndrome will be important to determine the use of the chemical senses as clinical markers of disease progression.

Plasma Neurofilament Light Chain Levels Are Elevated in Children and Young Adults With Wolfram Syndrome

“…Higher scores indicate more accurate smell identification. Relative to age-matched healthy controls and individuals with Type 1 diabetes, a sample ( n = 40) including most of the individuals with Wolfram syndrome in the current study had less accurate smell identification ( Alfaro et al, 2020 ).…”

“…Smell identification was assessed with the University of Pennsylvania Smell Identification Test ( Doty et al, 1984 ) as described in Alfaro et al (2020) . Briefly, participants were asked to scratch and sniff stimuli with microencapsulated odorants and indicate which of four response alternatives best matched the perceived odor.…”

Olfactory dysfunction and the role of stem cells in the regeneration of olfactory neurons

“…Olfactory dysfunction is classified into four main categories based on etiology and anatomical location: sensorineural olfactory dysfunction, conductive olfactory dysfunction, central olfactory dysfunction, and mixed olfactory dysfunction [ 18 ]. Sensorineural olfactory dysfunction results from inadequate reception or processing of stimuli by olfactory receptors, OSNs or the central nervous system's olfactory center, often associated with chronic inflammation, diabetes, aging, drug-induced and other factors [ [19] , [20] , [21] ].…”

Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome

“…[3][4][5] Previous studies have shown that Wolfram syndrome is associated with structural brain changes and multiple neurologic symptoms, eg, bladder dysfunction, gait and balance abnormalities, and loss of smell and taste sensations. [6][7][8][9] The pathophysiologic mechanisms underlying these neurologic manifestations are an area of active research.…”