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Magnetic Resonance Imaging (MRI) of the brain revealed the loss of posterior pituitary bright spot, suggesting the diagnosis of central diabetes insipidus.
Source publication
Purpose:
To report a case of Wolfram syndrome (WS) characterized by diabetes mellitus, diabetes insipidus, progressive optic atrophy, and deafness.
Case report:
A 19-year-old female patient, a known case of diabetes mellitus type I from six years before, presented with progressive vision loss since four years earlier. On fundoscopic examination,...
Context in source publication
Context 1
... 100 mcg three times daily. A few days later, the volume of urine collected in 24 h was within acceptable range. A Magnetic Resonance Imaging (MRI) of the brain revealed the loss of the physiological hyperintense signal of the posterior pituitary gland (bright spot) on T1-weighted images, suggesting the diagnosis of central diabetes insipidus (Fig. ...Similar publications
Background
Wolfram's syndrome (WFS) is a hereditary (autosomal recessive) neurodegenerative disorder. The clinical features are related to diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) with other variable clinical manifestations. Pathogenic variants in the WFS1 gene, encoding wolframin, are known to be the main cause...
Wolfram syndrome (WS) is a rare genetic disorder typically characterized by juvenile onset diabetes mellitus, optic atrophy, hearing loss, diabetes insipidus, and neurodegeneration. There would be a high index of clinical suspicion for WS when clinical manifestations of type 1 diabetes and optic atrophy present together. Genetic analysis is often r...
Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity...
Background:
Wolfram syndrome (WS) is a rare autosomal recessive disorder associated with early-onset diabetes mellitus (DM), diabetes insipidus (DI), optic atrophy (OA) and hearing impairment. Most patients with WS have mutations in the WFS1 gene, which encodes wolframin. This case report describes a patient with a novel heterozygous mutation of WF...
Wolfram syndrome (WFS) is an autosomal recessive neurodegenerative disorder, 90% of which is caused by loss of function of the endoplasmic reticular membrane protein Wolframin or WFS 1. Wolfram syndrome results in Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness (DIDMOAD) in humans. In mammalian cells WFS1 interacts with the ER-lo...
Citations
... It is also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) and is defined by juvenile onset nonimmune insulin dependent diabetes mellitus, progressive bilateral optic nerve atrophy, and sensorineural hearing loss. 1,2,3 Urinary tract, neurological, reproductive, and psychological problems may be linked to Wolfram syndrome. This disease's pathophysiology is still a mystery. ...
... This disease's pathophysiology is still a mystery. 1,2 The wolfram syndrome mutant gene (WFS1) has been located on chromosome 4p 16.1, however there is evidence of locus heterogeneity and mutations in mitochondrial genes in a small number of documented cases. 4,5 In the UK, 1/770.000 ...
... Less than 8% of the 300 patients described in the literature from all around the globe had diabetic retinopathy as a side effect of wolfram syndrome. 1 There are, however, just a few sources that describe the relationship of cataracts with this disease. This case report describes the first case of Wolfram syndrome in a Saudi family, which manifested as proliferative diabetic retinopathy and a powder-like cataract, among other uncommon ophthalmological findings. ...
Wolfram syndrome, also known as DIDMOAD or juvenile onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, and deafness, is a genetic neurological condition. This case report provides a description on the first instance of Wolfram syndrome in a Saudi family, which manifested as proliferative diabetic retinopathy and a powder-like cataract, among the other unusual ophthalmological findings. This case involved a 27-year-old Saudi woman with bilateral optic nerve atrophy who was first diagnosed with diabetes mellitus at the age of 8 years. At the age of 18, bilateral optic nerve atrophy was identified. At the age of 27, diabetes insipidus and hearing loss were verified. There were no signs of renal, neurological, or psychiatric issues. Atypical ophthalmological traits were examined and addressed in this study. Any individual with bilateral optic nerve atrophy and insulin-dependent diabetes mellitus within the first 30 years of life should be evaluated for the possibility of Wolfram syndrome. Microvascular diabetes is an incredibly rare complication of Wolfram syndrome. Early diagnosis, treatment, and prevention of severe consequences can result in improved survival rates and quality of life.
... Ключові слова: нецукровий діабет, цукровий діабет, дивертикулярна хвороба, постковідні ускладнення, пацієнт із коморбідністю. Вивчення взаємозв'язку і взаємозумовленості виявів COVID-19 в осіб із коморбідними захворюваннями є актуальними й дискусійними питаннями [3,10,13,17,20]. Триває вивчення патогенезу COVID-19, але, на думку експертів, постковідні вияви спричинені не лише подібністю механізмів етіопатогенетичної дії вірусу SARS-CoV-2 [15,19]. ...
... 07.02.2021 p. антитіла IgM до нуклеокапсидного антигену SARS-CoV-2 (SARS-CoV-2-NP-IgM) не виявлено. 10.02.2021 р. загальний аналіз крові: лейкоцитоз (лейкоцити -15,36 · 10 9 /л (норма -4,0 -9,0 · 10 9 /л)), тромбоцитоз (тромбоцити -458 · 10 9 /л (норма -150 -350 · 10 9 /л)), відсоток тромбоцитів -0,36 % (норма -0,15 -0,35 %), лейкоцитарна формула -без відхилень від референтних показників, ШОЕ -6 мм/год (норма -2 -15 мм/год). ...
... Копрограма: кількість -10 г, несформований, кашкоподібної консистенції, світло-коричневого кольору із різким запахом, «+» рослинна клітковина, що не перетравлюється, «++» не змінені м'язові волокна, «+++» змінені (перетравлені) м'язові волокна. 10.02.2021 р. Загальний аналіз сечі: ознаки гіпостенурії (питома вага -1001 при нормі 1001 -1040), що може свідчити про недостатню дозу замісної гормональної терапії виявів НД унаслідок розвитку постковідних ускладнень. ...
Cпорадично трапляються випадки поєднання гастроентерологічної патології з ендокринопатіями, пов’язані з глобальною пандемією коронавірусної хвороби‑2019 (COVID‑19). Тому вважаємо за доцільне навести унікальний клінічний випадок коморбідності захворювань після перенесеної COVID‑19. Пацієнтка К., 68 років, яка протягом п’яти років хворіла на нецукровий діабет та щоденно отримувала належне лікування (десмопресин), протягом 28 днів перебувала на стаціонарному лікуванні в центрі легеневих захворювань обласного фтизіопульмонологічного центру з приводу тяжкого перебігу COVID‑19. Через 2 міс після виписки зі стаціонару у зв’язку із переважаючими скаргами з боку ШКТ (біль за ходом товстого кишечника, рідкі випорожнення до 7 разів на добу, сухість у ротовій порожнині, сечовипускання до 3 разів уночі (ніктурія), загальна слабкість), що потребувало ретельної дифенційної діагностики, вона була госпіталізована в гастроентерологічне відділення обласної клінічної лікарні, де було встановлено діагноз тяжких постковідних ускладнень — дивертикулярної хвороби кишечника та цукрового діабету 2 типу, через що вона була переведена в хірургічне відділення. Актуальними є питання пошуку та удосконалення методів ранньої діагностики постковідних станів, що потенціюють розвиток поліморбідності. Патогенетично обґрунтований підхід до призначення терапії сприятиме зниженню захворюваності та смертності серед осіб із коморбідними захворюваннями. Коронавірусна пандемія змушує об’єднати зусилля медичної і наукової спільноти для дослідження нового коморбідного стану. Основним завданням мультидисциплінарних команд лікарів слід вважати вчасну діагностику відносно нових і маловивчених постковідних хвороб. Перспективами наукових досліджень є вивчення різноманітності клінічного перебігу, розробка та вдосконалення алгоритмів лікування і профілактики тяжких ускладнень дивертикулярної хвороби кишечника у поєднанні із нецукровим та цукровим діабетом.
... It is worth noting that ocular atrophy is intricately connected with Refsum disease, Friedreich's ataxia, Alstrom syndrome, Kearns-Sayre syndrome, Lawrence-Moon syndrome, as well as deafness and diabetes in individuals with the "3243" mitochondrial DNA alterations. Furthermore, diabetes mellitus has been observed to be associated with certain conditions mentioned above 49 . ...
Wolfram syndrome is a rare neurological disorder characterised by four main symptoms: diabetes mellitus, optic atrophy, deafness, and diabetes insipidus. It is caused by alterations in the CISD2 and WFS1 genes, which encode important proteins involved in cellular processes. Wolfram syndrome type 1 (WS1) has an earlier onset of diabetes and more severe neurological and ocular involvement compared to WS2. The diagnosis of Wolfram syndrome is based on the presence of early-onset diabetes and progressive optic atrophy. Genetic analysis, such as sequencing of the WFS1 gene, is used to confirm the diagnosis. The prevalence of Wolfram syndrome varies across populations, with a carrier frequency of 1 in 354. Individuals with Wolfram syndrome may experience a range of complications, including neurological abnormalities, urinary tract problems, depression, and an increased risk of suicide. The pathophysiology of Wolfram syndrome involves endoplasmic reticulum stress and unfolded protein responses, leading to cellular dysfunction and apoptosis. A differential diagnosis includes other genetic and mitochondrial disorders with similar symptoms. Although there is no cure for Wolfram syndrome, careful clinical observation and supportive therapy can help manage the symptoms and improve the quality of life for affected individuals.
... In addition, there are other several systemic manifestations such as urinary abnormalities (hydroureter and hydronephrosis among others), neurological signs (ataxia, cognitive impairment), endocrine disorders (deficient growth hormone and corticotropin secretion, hypogonadism in man and delayed menarche in female), and psychiatric symptoms (ranging from mood swings, panic attacks and sleep abnormalities to severe depression) [7]. In fact, the association between DM and OA is the most common clinical finding of WS and the diagnosis should be suspected in the absence of either complete clinical findings [11]. ...
Background
Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by juvenile onset diabetes, optic nerve atrophy and other systemic manifestations. Symptoms of the disease arise mostly in early childhood with a high mortality rate due to severe neurological complications. Two causative genes have been identifed in this syndrome; the classical form is caused by autosomal recessive mutations of the WFS1 gene, and a smaller portion of patients has mutations in the CIDS2 gene, which are responsible for autosomal recessive Wolfram syndrome 2.
Case presentation
We report the case of a 28-year-old Moroccan boy born from consanguineous parents referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of Wolfram syndrome was made based on insulin-dependent diabetes, optic nerve atrophy, sensorineural deafness, urological abnormalities and psychiatric illness. To establish the diagnosis at a molecular level, we performed next-generation sequencing in the index patient, which revealed compound heterozygous WFS1 mutations: c.1113G > A (p.Trp371Ter) and c.1223_1224insGGAACCACCTGGAGCCCTATGCCCATTT (p.Phe408fs). This second variant has never been described in patients with Wolfram syndrome.
Conclusion
The identification of the genetic substrate in our patient confirmed the clinical diagnosis of Wolfram syndrome and allowed us to provide him an appropriate management and genetic counseling to his family.
... Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder that minimally requires the presence of two diagnostic criteria, insulin-dependent diabetes mellitus (IDDM) and progressive optic nerve atrophy. [1] WS is variably associated with diabetes insipidus, neurological disorders, urinary tract anomalies, endocrine dysfunctions and many other systemic manifestations. Wolfram and Wagener first described WS in 1938. ...
... Currently, there are 400-500 million DM patients worldwide 1,2 . Numerous studies have indicated that one of the leading causes of DM-induced body damage is the development of complications including ocular complications, diabetic foot, and cardio-cerebrovascular complications 3 . As a severe ocular complication, diabetic retinopathy (DR) is a major cause of acquired blindness in adults 4,5 . ...
OBJECTIVE: The aim of this study was to investigate the relationships of aquaporin 4 (AQP4) rs200498749, rs149465 and rs650217 polymorphisms and gene expression with diabetic retinopathy (DR).
PATIENTS AND METHODS: A total of 400 patients with diabetes mellitus (DM) treated in our hospital were enrolled in this study. All subjects were divided into two groups, including DM group (n=200, without DR) and DR group (n=200, with DR). The polymorphisms rs200498749, rs149465 and rs650217 of AQP4 gene were analyzed in the two groups. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect gene expression, and statistical analysis was performed in combination with clinical data.
RESULTS: The distribution of alleles of AQP4 rs650217 (p=0.015) in DR group was different from that in DM group, and the frequency of T allele was significantly higher in DR group than DM group. The distribution of genotypes of AQP4 rs149465 (p=0.000) and rs650217 (p=0.000) showed statistically significant difference between DR group and DM group. The frequency of AA genotype of polymorphism rs149465 and CT genotype of polymorphism rs650217 was significantly higher in DR group than DM group. Besides, there was a difference in the distribution of recessive models of AQP4 rs149465 (p=0.023) and rs650217 (p=0.014) between DR group and DM group. DR group exhibited remarkably lowered frequency of AA + AT recessive model of the polymorphism rs149465 and raised frequency of CT + TT recessive model of the polymorphism rs650217. Similarly, a difference was found in the distribution of haplotypes CAT (p=0.014) and CTC (p=0.003) of AQP4 rs200498749, rs149465 and rs650217 between DR group and DM group. The polymorphism rs200498749 of AQP4 gene was significantly correlated with AQP4 gene expression (p
... Kaempferol, a natural flavonol, possesses numerous pharmacological properties, including antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective and antidiabetic activities [1,2]. Diabetes mellitus is generally characterized by hyperglycaemia and poor metabolism of carbohydrates, fats, and proteins [3]. Roughly, 422 million of global adult population were suffering from this endocrinal disorder in 2014 [4]. ...
In this study, complexes of kaempferol (KF) with polysaccharide arabinogalactan (AG) and disodium glycyrrhizinate (Na2GA) were prepared through mechanochemical technique to improve the solubility and bioavailability of KF. The physicochemical properties and the interactions of KF with AG/Na2GA were investigated through dissolution, SEM, XRD and DSC studies. The reduction of particle sizes and destroy of crystal forms revealed the formation of solid dispersion which may have assisted the dissolution of the drug. The accelerated stability study showed higher stability for KF-Na2GA complex. In vivo pharmacokinetic study was performed to observe the plasma drug concentrations for KF complexes. Mechanochemical complexation of KF with AG/Na2GA improved the pharmacological activity as evident by the inhibitory potential of the complexes towards carbohydrate metabolic enzymes. In vivo studies were performed in STZ-induced diabetic mice, where the group treated with KF-AG complex showed better liver and kidney function and lower blood glucose levels than pure KF. Therefore, mechanochemical complexes of KF with polysaccharide or glycyrrhizate may serve as a promising formulation for the treatment of diabetes.
An 11-year-old male child who presented with increased frequency of urination, thirst and feeling of incomplete void was initially diagnosed with diabetes mellitus (DM) based on elevated blood sugar. Polyuria and polydipsia were confirmed even after normalisation of blood sugar. A standardised water deprivation test showed presence of central diabetes insipidus (DI) and patient was started on desmopressin. Presence of DM and DI led to suspicion of DIDMOAD/Wolfram syndrome and ophthalmic examination confirmed bilateral optic atrophy. Despite treatment for DM and DI the urinary complaints persisted, and ultrasound showed persistent bilateral hydronephroureterosis. Bladder workup including voiding cystourethrography (VCUG) and urodynamic study reported thickened trabeculated bladder wall along with overactivity, poor compliance and high bladder pressure. Bladder dysfunction has been documented to be associated with Wolfram syndrome and often may lead to chronic kidney disease which can be prevented by early diagnosis and appropriate management. The case highlights the need for comprehensive evaluation of children with urinary symptoms.
Background:
Wolfram syndrome type 1 is a rare neurodegenerative disorder including diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, with variable additional findings. The phenotypic spectrum is very heterogeneous, with non-autoimmune juvenile-onset diabetes and optic atrophy as minimal criteria for the diagnosis. Biallelic mutations in the WFS1 gene are the causative genetic anomaly for the syndrome, with, however, no evident genotype-phenotype correlation. Among the clinical features of the disease, diabetic retinopathy depicts a rarely reported microvascular complication. In this report, we describe the clinical and genetic findings in a 26-year-old patient presenting with Wolfram syndrome and severe diabetic retinopathy.
Methods:
The mutation screening was performed by polymerase chain reaction followed by Sanger sequencing of the entire coding sequence of the WFS1 gene.
Results:
A novel homozygous missense variant c.1901A>T (p.Lys634Met) was found in the proband and classified as probably pathogenic according to the American College of Medical Genetics and Genomics.
Conclusions:
The molecular study of the WFS1 gene is essential for the diagnostic confirmation, to provide appropriate genetic counseling and a mutational screening in the at-risk relatives. The c.1901A>T (p.Lys634 Met) is a novel variant that could be responsible for a severe form of Wolfram syndrome with early and proliferative diabetic retinopathy.
