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Agnieszka Zmyslowska - One of the best experts on this subject based on the ideXlab platform.
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reduced corneal sensitivity with neuronal degeneration is a novel clinical feature in Wolfram Syndrome
American Journal of Ophthalmology, 2021Co-Authors: Arleta Waszczykowska, Agnieszka Zmyslowska, Sulev Kõks, Piotr Jurowski, Krzysztof Bartosiewicz, Maciej Studzian, łukasz Pulaski, Marcin Braun, Marilin Ivask, Wojciech MlynarskiAbstract:Abstract Purpose : To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram Syndrome (WFS). Design and Setting : An observational clinical case series with confirmatory experiments. Participants : A group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D). Methods : All subjects (n=42) underwent a complete ophthalmic examination, esthesiometry and retinal nerve fiber layer assessment using optical coherence tomography. Morphological assessment of corneal neuropathy by in vivo corneal confocal microscopy (IVCCM) was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (one eye) as well as in 24 T1D patients (both eyes in 6 patients and one eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type (Wfs1WT) littermates were subjected to laser scanning confocal microscopy (LSCM). Results : Corneal sensitivity was significantly reduced in WFS patients compared to T1D patients (4.50 (3.50-5.50) cm vs. 6.00 (6.00-6.00) cm; p Conclusions : Reduced corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.
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optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram Syndrome
Developmental Medicine & Child Neurology, 2019Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Arleta Waszczykowska, Wojciech Fendler, Dobromila Baranska, Konrad Stawiski, Piotr Jurowski, Wojciech MlynarskiAbstract:AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram Syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram Syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.
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serum metabolic fingerprinting identified putatively annotated sphinganine isomer as a biomarker of Wolfram Syndrome
Journal of Proteome Research, 2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients w...
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Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome
2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients
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RESEARCH ARTICLE Central Nervous System PET-CT Imaging Reveals Regional Impairments in Pediatric Patients with Wolfram Syndrome
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Wojciech Fendler, Dobromila Baranska, Wojciech Mlynarski, Bogdan Malkowski, Piotr Gnys, Citation Zmyslowska A, Malkowski BAbstract:. These authors contributed equally to this work. Wolfram Syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9¡2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8¡4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups,13 years old and.13 years old to account for developmental differences
Maciej Borowiec - One of the best experts on this subject based on the ideXlab platform.
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optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram Syndrome
Developmental Medicine & Child Neurology, 2019Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Arleta Waszczykowska, Wojciech Fendler, Dobromila Baranska, Konrad Stawiski, Piotr Jurowski, Wojciech MlynarskiAbstract:AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram Syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram Syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.
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serum metabolic fingerprinting identified putatively annotated sphinganine isomer as a biomarker of Wolfram Syndrome
Journal of Proteome Research, 2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients w...
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Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome
2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients
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RESEARCH ARTICLE Central Nervous System PET-CT Imaging Reveals Regional Impairments in Pediatric Patients with Wolfram Syndrome
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Wojciech Fendler, Dobromila Baranska, Wojciech Mlynarski, Bogdan Malkowski, Piotr Gnys, Citation Zmyslowska A, Malkowski BAbstract:. These authors contributed equally to this work. Wolfram Syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9¡2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8¡4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups,13 years old and.13 years old to account for developmental differences
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ORIGINAL ARTICLE Glycemic variability in patients with Wolfram Syndrome is lower than in type 1 diabetes
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Wojciech Fendler, A. Szadkowska, M. Mysliwiec, A. Baranowska-jazwiecka, M. Buraczewska, M. Fulmanska-anders, B. Mianowska, I. PietrzakAbstract:Aims Wolfram Syndrome (WFS) is diagnosed as coexis-tence of diabetes mellitus and optic atrophy, where pan-creatic beta cell destruction is associated with neurodegeneration. Typically, WFS necessitates insulin treatment similar to type 1 diabetes (T1D), but the mechanism of beta cell mass reduction leading to hyper-glycemia is different. Methods The aim of the study was to assess glycemic variability using the continuous glucose monitoring (CGM) system in seven pediatric patients with genetically con-firmed WFS and compare the results with data obtained from 21 propensity score-matched patients with T1D. The ‘‘GlyCulator’ ’ application was used for the calculation of glycemic variability indices. Results CGM recordings showed similarities in glycemic variability among WFS patients, but differing from those of the T1D group. Coefficient of variation (%CV), CON-GA4h, and GONGA6h were significantly (p \ 0.05) lower in WFS patients (28.08 ± 7.37, 54.96 ± 11.92, and 55.99 ± 10.58) than in T1D patients (37.87 ± 14.24
Wojciech Mlynarski - One of the best experts on this subject based on the ideXlab platform.
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reduced corneal sensitivity with neuronal degeneration is a novel clinical feature in Wolfram Syndrome
American Journal of Ophthalmology, 2021Co-Authors: Arleta Waszczykowska, Agnieszka Zmyslowska, Sulev Kõks, Piotr Jurowski, Krzysztof Bartosiewicz, Maciej Studzian, łukasz Pulaski, Marcin Braun, Marilin Ivask, Wojciech MlynarskiAbstract:Abstract Purpose : To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram Syndrome (WFS). Design and Setting : An observational clinical case series with confirmatory experiments. Participants : A group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D). Methods : All subjects (n=42) underwent a complete ophthalmic examination, esthesiometry and retinal nerve fiber layer assessment using optical coherence tomography. Morphological assessment of corneal neuropathy by in vivo corneal confocal microscopy (IVCCM) was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (one eye) as well as in 24 T1D patients (both eyes in 6 patients and one eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type (Wfs1WT) littermates were subjected to laser scanning confocal microscopy (LSCM). Results : Corneal sensitivity was significantly reduced in WFS patients compared to T1D patients (4.50 (3.50-5.50) cm vs. 6.00 (6.00-6.00) cm; p Conclusions : Reduced corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.
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optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram Syndrome
Developmental Medicine & Child Neurology, 2019Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Arleta Waszczykowska, Wojciech Fendler, Dobromila Baranska, Konrad Stawiski, Piotr Jurowski, Wojciech MlynarskiAbstract:AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram Syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram Syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.
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RESEARCH ARTICLE Central Nervous System PET-CT Imaging Reveals Regional Impairments in Pediatric Patients with Wolfram Syndrome
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Wojciech Fendler, Dobromila Baranska, Wojciech Mlynarski, Bogdan Malkowski, Piotr Gnys, Citation Zmyslowska A, Malkowski BAbstract:. These authors contributed equally to this work. Wolfram Syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9¡2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8¡4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups,13 years old and.13 years old to account for developmental differences
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Central Nervous System PET-CT Imaging Reveals Regional Impairments in Pediatric Patients with Wolfram Syndrome
2014Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Wojciech Fendler, Dobromila Baranska, Bogdan Malkowski, Piotr Gnys, Wojciech MlynarskiAbstract:Wolfram Syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9±2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8±4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups 13 years old to account for developmental differences. Reduced SUVs in WFS patients as compared to the control group for the bilateral brain regions such as occipital lobe (−1.24±1.20 vs. −0.13±1.05; p = 0.028) and cerebellum (−1.11±0.69 vs. −0.204±1.00; p = 0.036) were observed and the same tendency for cingulate (−1.13±1.05 vs. −0.15±1.12; p = 0.056), temporal lobe (−1.10±0.98 vs. −0.15±1.10; p = 0.057), parietal lobe (−1.06±1.20 vs. −0.08±1.08; p = 0.058), central region (−1.01±1.04 vs. −0.09±1.06; p = 0.060), basal ganglia (−1.05±0.74 vs. −0.20±1.07; p = 0.066) and mesial temporal lobe (−1.06±0.82 vs. −0.26±1.08; p = 0.087) was also noticed. After adjusting for multiple hypothesis testing, the differences in glucose uptake were non-significant. For the first time, regional differences in brain glucose metabolism among patients with WFS were shown using PET-CT imaging.
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Wolfram Syndrome in the polish population novel mutations and genotype phenotype correlation
Clinical Endocrinology, 2011Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Mieczyslaw Szalecki, A Stefanski, B Iwaniszewska, M Jedrzejczyk, Iwona Pietrzak, Wojciech MlynarskiAbstract:Summary Objective Wolfram Syndrome is a rare form of diabetes mellitus associated with optic atrophy and disorders of different organs (e.g. diabetes insipidus, hearing loss, ataxia, anaemia and many others). This Syndrome is caused by recessive mutations in the Wolframin gene (WFS1) localized on chromosome 4p16·1. The aim of this study was to identify the causative mutations in WFS1 in a group of Polish patients with suspected Wolfram Syndrome. Design Patients and Measurements: Nine patients with clinical symptoms consistent with Wolfram Syndrome (at least diabetes mellitus and optic atrophy) and 22 first-degree relatives were examined. The molecular analysis was carried out by direct sequencing of the exons, the exon–intron junctions, and the 5′ and 3′ untranslated regions of WFS1. Results Nine different mutations in WFS1 (five of them novel) were identified in the nine patients. Six patients were homozygous for the following mutations: V412fs, S443R, W539X, V659fs. They developed diabetes at a mean age of 5·2 years. Three patients were compound-heterozygous for the following mutations: S167fs, Q392X, Y513fs, W648X, V779G. They developed diabetes at a mean age of 6·5 years. Conclusions Mean age of diagnosis of diabetes among the Polish patients was typical for Wolfram Syndrome; however, compound-heterozygous patients were slightly older at diabetes onset.
Arleta Waszczykowska - One of the best experts on this subject based on the ideXlab platform.
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reduced corneal sensitivity with neuronal degeneration is a novel clinical feature in Wolfram Syndrome
American Journal of Ophthalmology, 2021Co-Authors: Arleta Waszczykowska, Agnieszka Zmyslowska, Sulev Kõks, Piotr Jurowski, Krzysztof Bartosiewicz, Maciej Studzian, łukasz Pulaski, Marcin Braun, Marilin Ivask, Wojciech MlynarskiAbstract:Abstract Purpose : To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram Syndrome (WFS). Design and Setting : An observational clinical case series with confirmatory experiments. Participants : A group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D). Methods : All subjects (n=42) underwent a complete ophthalmic examination, esthesiometry and retinal nerve fiber layer assessment using optical coherence tomography. Morphological assessment of corneal neuropathy by in vivo corneal confocal microscopy (IVCCM) was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (one eye) as well as in 24 T1D patients (both eyes in 6 patients and one eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type (Wfs1WT) littermates were subjected to laser scanning confocal microscopy (LSCM). Results : Corneal sensitivity was significantly reduced in WFS patients compared to T1D patients (4.50 (3.50-5.50) cm vs. 6.00 (6.00-6.00) cm; p Conclusions : Reduced corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.
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optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram Syndrome
Developmental Medicine & Child Neurology, 2019Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Arleta Waszczykowska, Wojciech Fendler, Dobromila Baranska, Konrad Stawiski, Piotr Jurowski, Wojciech MlynarskiAbstract:AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram Syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram Syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.
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serum metabolic fingerprinting identified putatively annotated sphinganine isomer as a biomarker of Wolfram Syndrome
Journal of Proteome Research, 2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients w...
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Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome
2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients
Wojciech Fendler - One of the best experts on this subject based on the ideXlab platform.
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optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram Syndrome
Developmental Medicine & Child Neurology, 2019Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Arleta Waszczykowska, Wojciech Fendler, Dobromila Baranska, Konrad Stawiski, Piotr Jurowski, Wojciech MlynarskiAbstract:AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram Syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram Syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.
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serum metabolic fingerprinting identified putatively annotated sphinganine isomer as a biomarker of Wolfram Syndrome
Journal of Proteome Research, 2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients w...
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Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome
2017Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Wojciech Fendler, Michal Ciborowski, Adam KretowskiAbstract:Wolfram Syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients
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RESEARCH ARTICLE Central Nervous System PET-CT Imaging Reveals Regional Impairments in Pediatric Patients with Wolfram Syndrome
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Karolina Antosik, Wojciech Fendler, Dobromila Baranska, Wojciech Mlynarski, Bogdan Malkowski, Piotr Gnys, Citation Zmyslowska A, Malkowski BAbstract:. These authors contributed equally to this work. Wolfram Syndrome (WFS) is inherited as an autosomal recessive disease with main clinical features of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. However, various neurological defects may also be detected. The aim of this study was to evaluate aspects of brain structure and function using PET-CT (positron emission tomography and computed tomography) and MRI (magnetic resonance imaging) in pediatric patients with WFS. Regional changes in brain glucose metabolism were measured using standardized uptake values (SUVs) based on images of (18F) fluorodeoxyglucose (FDG) uptake in 7 WFS patients aged 10.1–16.0 years (mean 12.9¡2.4) and in 20 healthy children aged 3–17.9 years (mean 12.8¡4.1). In all patients the diagnosis of WFS was confirmed by DNA sequencing of the WFS1 gene. Hierarchical clustering showed remarkable similarities of glucose uptake patterns among WFS patients and their differences from the control group. SUV data were subsequently standardized for age groups,13 years old and.13 years old to account for developmental differences
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ORIGINAL ARTICLE Glycemic variability in patients with Wolfram Syndrome is lower than in type 1 diabetes
2016Co-Authors: Agnieszka Zmyslowska, Maciej Borowiec, Wojciech Fendler, A. Szadkowska, M. Mysliwiec, A. Baranowska-jazwiecka, M. Buraczewska, M. Fulmanska-anders, B. Mianowska, I. PietrzakAbstract:Aims Wolfram Syndrome (WFS) is diagnosed as coexis-tence of diabetes mellitus and optic atrophy, where pan-creatic beta cell destruction is associated with neurodegeneration. Typically, WFS necessitates insulin treatment similar to type 1 diabetes (T1D), but the mechanism of beta cell mass reduction leading to hyper-glycemia is different. Methods The aim of the study was to assess glycemic variability using the continuous glucose monitoring (CGM) system in seven pediatric patients with genetically con-firmed WFS and compare the results with data obtained from 21 propensity score-matched patients with T1D. The ‘‘GlyCulator’ ’ application was used for the calculation of glycemic variability indices. Results CGM recordings showed similarities in glycemic variability among WFS patients, but differing from those of the T1D group. Coefficient of variation (%CV), CON-GA4h, and GONGA6h were significantly (p \ 0.05) lower in WFS patients (28.08 ± 7.37, 54.96 ± 11.92, and 55.99 ± 10.58) than in T1D patients (37.87 ± 14.24
