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International Journal of Environmental... Nov 2021Wolfram Syndrome (WS) is a rare neurodegenerative disease with autosomal recessive inheritance and characterized by juvenile onset, non-autoimmune diabetes mellitus and... (Review)
Review
Wolfram Syndrome (WS) is a rare neurodegenerative disease with autosomal recessive inheritance and characterized by juvenile onset, non-autoimmune diabetes mellitus and later followed by optic atrophy leading to blindness, diabetes insipidus, hearing loss, and other neurological and endocrine dysfunctions. A wide spectrum of neurodegenerative abnormalities affecting the central nervous system has been described. Among these complications, neurogenic bladder and urodynamic abnormalities also deserve attention. Urinary tract dysfunctions (UTD) up to end stage renal disease are a life-threatening complication of WS patients. Notably, end stage renal disease is reported as one of the most common causes of death among WS patients. UTD have been also reported in affected adolescents. Involvement of the urinary tract occurs in about 90% of affected patients, at a median age of 20 years and with peaks at 13, 21 and 33 years. The aim of our narrative review was to provide an overview of the most important papers regarding urological impairment in Wolfram Syndrome. A comprehensive search on PubMed including Wolfram Syndrome and one or more of the following terms: chronic renal failure, bladder dysfunction, urological aspects, and urinary tract dysfunction, was done. The exclusion criteria were studies not written in English and not including urinary tract dysfunction deep evaluation and description. Studies mentioning general urologic abnormalities without deep description and/or follow-up were not considered. Due to the rarity of the condition, we considered not only papers including pediatric patients, but also papers with pediatric and adult case reports.
Topics: Adolescent; Adult; Child; Humans; Neurodegenerative Diseases; Optic Atrophy; Urinary Tract; Urodynamics; Wolfram Syndrome; Young Adult
PubMed: 34831749
DOI: 10.3390/ijerph182211994 -
Orphanet Journal of Rare Diseases Aug 2019Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep...
BACKGROUND
Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.
METHODS
Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements.
RESULTS
Twenty-one patients were evaluated ranging from age 8.9-29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI's ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients' scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders.
CONCLUSIONS
Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.
Topics: Adolescent; Adult; Female; Humans; Magnetic Resonance Imaging; Male; Sleep Wake Disorders; Surveys and Questionnaires; Wolfram Syndrome; Young Adult
PubMed: 31375124
DOI: 10.1186/s13023-019-1160-z -
American Journal of Kidney Diseases :... Oct 2016Pemetrexed is an approved antimetabolite agent, now widely used for treating locally advanced or metastatic nonsquamous non-small cell lung cancer. Although no...
Pemetrexed is an approved antimetabolite agent, now widely used for treating locally advanced or metastatic nonsquamous non-small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed.
Topics: Adult; Antineoplastic Agents; Diabetes Insipidus, Nephrogenic; Humans; Male; Pemetrexed
PubMed: 27241854
DOI: 10.1053/j.ajkd.2016.04.016 -
Science Translational Medicine Feb 2022The Wolfram syndrome is a rare autosomal recessive disease affecting many organs with life-threatening consequences; currently, no treatment is available. The disease is...
The Wolfram syndrome is a rare autosomal recessive disease affecting many organs with life-threatening consequences; currently, no treatment is available. The disease is caused by mutations in the gene, coding for the protein wolframin, an endoplasmic reticulum (ER) transmembrane protein involved in contacts between ER and mitochondria termed as mitochondria-associated ER membranes (MAMs). Inherited mutations usually reduce the protein's stability, altering its homeostasis and ultimately reducing ER to mitochondria calcium ion transfer, leading to mitochondrial dysfunction and cell death. In this study, we found that activation of the sigma-1 receptor (S1R), an ER-resident protein involved in calcium ion transfer, could counteract the functional alterations of MAMs due to wolframin deficiency. The S1R agonist PRE-084 restored calcium ion transfer and mitochondrial respiration in vitro, corrected the associated increased autophagy and mitophagy, and was able to alleviate the behavioral symptoms observed in zebrafish and mouse models of the disease. Our findings provide a potential therapeutic strategy for treating Wolfram syndrome by efficiently boosting MAM function using the ligand-operated S1R chaperone. Moreover, such strategy might also be relevant for other degenerative and mitochondrial diseases involving MAM dysfunction.
Topics: Animals; Calcium; Female; Humans; Male; Mice; Receptors, sigma; Wolfram Syndrome; Zebrafish; Sigma-1 Receptor
PubMed: 35138910
DOI: 10.1126/scitranslmed.abh3763 -
The Indian Journal of Medical Research Sep 2018
Topics: Antidiuretic Agents; Antineoplastic Agents; Biopsy; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Mercaptopurine; Pituitary Gland; Prednisolone; Skin; Treatment Outcome; Vinblastine
PubMed: 30425231
DOI: 10.4103/ijmr.IJMR_1988_16 -
Stem Cell Reports May 2023Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases,...
Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients. VDAC1 is identified to interact with WFS1, whereas loss of this interaction in WS cells could compromise mitochondrial function. Restoring WFS1 levels in WS cells reinstates WFS1-VDAC1 interaction, which correlates with an increase in MAMs and mitochondrial network that could positively affect mitochondrial function. Genetic rescue by WFS1 overexpression or pharmacological agents modulating mitochondrial function improves the viability and bioenergetics of WS neurons. Our data implicate a role of WFS1 in regulating mitochondrial functionality and highlight a therapeutic intervention for WS and related rare diseases with mitochondrial defects.
Topics: Humans; Wolfram Syndrome; Induced Pluripotent Stem Cells; Neurodegenerative Diseases; Membrane Proteins; Neurons; Mitochondria; Mutation
PubMed: 37163979
DOI: 10.1016/j.stemcr.2023.04.002 -
Trends in Pharmacological Sciences Oct 2019Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and... (Review)
Review
Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum disorder.
Topics: Animals; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Genetic Therapy; Humans; Molecular Targeted Therapy; Regenerative Medicine; Wolfram Syndrome
PubMed: 31420094
DOI: 10.1016/j.tips.2019.07.011 -
The Journal of Clinical Endocrinology... May 2022Copeptin derives from the same precursor peptide preprovasopressin as arginine vasopressin (AVP). The secretion of both peptides is stimulated by similar physiological...
Copeptin derives from the same precursor peptide preprovasopressin as arginine vasopressin (AVP). The secretion of both peptides is stimulated by similar physiological processes, such as osmotic stimulation, hypovolemia, or stress. AVP is difficult to measure due to complex preanalytical requirements and due to technical difficulties. In the last years, copeptin was found to be a stable, sensitive, and simple to measure surrogate marker of AVP release. Different immunoassays exist to measure copeptin. The 2 assays which have most often be used in clinical studies are the original sandwich immunoluminometric assay and its automated immunofluorescent successor. In addition, various enzyme-linked immunosorbent assay have been developed. With the availability of the copeptin assay, the differential diagnosis of diabetes insipidus was recently revisited. The goal for this article is therefore to first review the physiology of copeptin, and second to describe its use as marker for the differential diagnosis of vasopressin-dependent fluid disorders, mainly diabetes insipidus but also hyper- and hyponatremia. Furthermore, we highlight the role of copeptin as prognostic marker in other acute and chronic diseases.
Topics: Arginine Vasopressin; Biomarkers; Diabetes Insipidus; Glycopeptides; Humans; Hyponatremia
PubMed: 35137148
DOI: 10.1210/clinem/dgac070 -
Frontiers in Endocrinology 2022To describe the urinary tract characteristics of diabetes insipidus (DI) patients with upper urinary tract dilatation (UUTD) using the video-urodynamic recordings...
OBJECTIVE
To describe the urinary tract characteristics of diabetes insipidus (DI) patients with upper urinary tract dilatation (UUTD) using the video-urodynamic recordings (VUDS), UUTD and all urinary tract dysfunction (AUTD) systems, and to summarize the experience in the treatment of DI with UUTD.
METHODS
This retrospective study analyzed clinical data from 26 patients with DI, including micturition diary, water deprivation tests, imaging data and management. The UUTD and AUTD systems were used to evaluate the urinary tract characteristics. All patients were required to undergo VUDS, neurophysiologic tests to confirm the presence of neurogenic bladder (NB).
RESULTS
VUDS showed that the mean values for bladder capacity and bladder compliance were 575.0 ± 135.1 ml and 51.5 ± 33.6 cmHO in DI patients, and 42.3% (11/26) had a post-void residual >100 ml. NB was present in 6 (23.1%) of 26 DI patients with UUTD, and enterocystoplasty was recommended for two patients with poor bladder capacity, compliance and renal impairment. For the 24 remaining patients, medication combined with individualized and appropriate bladder management, including intermittent catheterization, indwelling catheter and regular voiding, achieved satisfactory results. High serum creatinine decreased from 248.0 ± 115.8 μmoI/L to 177.4 ± 92.8 μmoI/L in 12 patients from a population with a median of 108.1 μmoI/L (IQR: 79.9-206.5 μmoI/L). Forty-four dilated ureters showed significant improvement in the UUTD grade, and the median grade of 52 UUTD ureters decreased from 3 to 2.
CONCLUSION
Bladder distension, trabeculation and decreased or absent sensations were common features for DI patients with UUTD. Individualized therapy by medication combined with appropriate bladder management can improve UUTD and renal function in DI patients.
Topics: Diabetes Insipidus; Diabetes Mellitus; Dilatation; Humans; Retrospective Studies; Urinary Bladder, Neurogenic; Urinary Tract
PubMed: 35937824
DOI: 10.3389/fendo.2022.941453 -
The Journal of International Medical... Nov 2018The prevalence of juvenile-onset gout has been increasing. Hereditary factors and secondary diseases should be considered in these patients. Adipsic diabetes insipidus... (Review)
Review
The prevalence of juvenile-onset gout has been increasing. Hereditary factors and secondary diseases should be considered in these patients. Adipsic diabetes insipidus (ADI) is characterized by arginine vasopressin (AVP) deficiency, which results in hypotonic polyuria, and dysfunction of thirst osmoreceptors, which results in failure to generate a thirst sensation in response to hypernatremia. We herein report a case of a boy with gouty arthritis, refractory hyperuricemia, prominent hypernatremia, a high creatinine concentration, and a history of surgery for a hypothalamic hamartoma. The patient was diagnosed with central diabetes insipidus after endocrine evaluation. Because he never had symptoms of thirst, the final diagnosis was corrected to ADI. This is the first report of gout due to chronic ADI in an adolescent. Volume contraction due to ADI might be one cause of hyperuricemia and renal impairment in such patients. Moreover, AVP deficiency might directly lead to low urate clearance due to the lack of vasopressin receptor 1 stimulation. Lack of polydipsia and polyuria may delay the diagnosis of ADI and lead to severe complications of a chronic hyperosmolar status. Sufficient and effective establishment of normovolemia is critical for these patients.
Topics: Adolescent; Diabetes Insipidus; Gout; Humans; Hyperuricemia; Joints; Kidney Diseases; Male
PubMed: 30270804
DOI: 10.1177/0300060518800114