Diabetes mellitus, diabetes insipidus, optic atrophy, and deafness: A case of Wolfram (DIDMOAD) syndrome

Maleki, Nasrollah; Bashardoust, Bahman; Zakeri, Anahita; Salehifar, Azita; Tavosi, Zahra

doi:10.1016/j.joco.2015.11.003

Cited by 9 publications

(3 citation statements)

References 30 publications

(35 reference statements)

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“…The mean age of diagnosis of OA in our patients was also 11.1 years (range 8–20). Besides OA, constriction of visual fields and declined VA and color vision are the other ophthalmological findings [1-3, 5, 9]. None of our patients had diabetic retinopathy, as it is described in the literature [9, 10].…”

Section: Discussionsupporting

confidence: 62%

Ophthalmologic Manifestations of Wolfram Syndrome: Report of 14 Cases

et al. 2018

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Purpose: The aim of this study was to describe ophthalmological abnormalities in 14 cases of Wolfram syndrome belonging to 9 different families. Methods: Patients were submitted to a complete ophthalmological, neurological, otorhinolaryngological, urological, and genetic evaluation. Results: Our sample comprised 14 Caucasian patients belonging to 9 different families. Their ages ranged from 10 to 38 years. The mean duration of known disease was 11.3 ± 8.7 years. Genetic confirmation was obtained in 7 families. There was a parental consanguinity history in 2 families. Five families were homozygous for a mutation of exon 8 of the WFS1 gene (Chr. 4), and 2 patients were heterozygous. Diabetes mellitus was the first manifestation in all except 1 patient. The mean age at diagnosis was 8.7 years (range 3–22). None had diabetic retinopathy. The mean age at diagnosis of optic atrophy was 11.1 years (range 8–35). The best-corrected visual acuity ranged from counting fingers to 20/50. Conclusions: Association of optic atrophy with insulin-dependent diabetes mellitus should raise the suspicion of Wolfram syndrome.

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Section: Discussionsupporting

confidence: 62%

Ophthalmologic Manifestations of Wolfram Syndrome: Report of 14 Cases

et al. 2018

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

Next generation sequencing identifies a pathogenic mutation of WFS1 gene in a Moroccan family with Wolfram syndrome: a case report

Sahli,

Zrhidri,

Boualaoui

et al. 2023

J Med Case Reports

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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.

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“…Wolfram Syndrome is an autosomal recessive progressive disease in which patients experience altered physical and psychological functions. The cardinal manifestations include diabetes mellitus coexisting with diabetes insipidus, bilateral optic atrophy, hearing and vision loss along with progressive motor, autonomic and psychiatric abnormalities ( 1 , 2 ). Wolfram Syndrome is also known by the acronym DIDMOAD (diabetes insipidus, insulin-deficient diabetes mellitus, optic atrophy and deafness) ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Mutations in Wolframin on Psychiatric Disorders

et al. 2021

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Wolfram Syndrome is a rare autosomal recessive disease characterized by early-onset diabetes mellitus, neurodegeneration, and psychological disorders. Mutations in the gene WFS1, coding for the protein wolframin, cause Wolfram Syndrome and are associated with bipolar disorder and schizophrenia. This report aims to connect WFS1 mutations to their impact on protein expression and structure, which ultimately translates to altered cell function and behavioral alterations of an individual.Methods: Published data were used to compile WFS1 mutations associated with psychiatric symptoms, both in homozygous patients and heterozygous carriers of WFS1 mutations. These mutations were evaluated in silico using SNAP2, PolyPhen-2, and PROVEAN to predict the effects of sequence variants. Statistical analysis was performed to assess the correlation between the locations of the mutations and the damage prediction scores.Results: Several mutations, clustering in the center and C-terminus of the WFS1 polypeptide, such as A559T and R558C, are found in individuals with psychiatric diseases and appear particularly impactful on protein structure. Our analysis showed that mutations in all regions of wolframin were present in patients with schizophrenia whereas only cytoplasmic and ER luminal mutations were reported in patients with manic episodes and bipolar disorders. According to Poly-Phen-2 predictions, 82.4% of the ER lumen mutations and 85.7% of the membrane mutations are damaging.Conclusion: We propose mood disorders in Wolfram Syndrome and heterozygous carriers of WFS1 mutations are the consequence of specific mutations in WFS1 that alter the structure of wolframin, resulting in intracellular calcium dysregulations and impaired cell signaling, Understanding the effect of WFS1 mutations on bipolar disorder and schizoprenia is integral to designing clinically targeted treatments for both diseases, which need more specialized treatments.

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Diabetes mellitus, diabetes insipidus, optic atrophy, and deafness: A case of Wolfram (DIDMOAD) syndrome

Cited by 9 publications

References 30 publications

Ophthalmologic Manifestations of Wolfram Syndrome: Report of 14 Cases

Ophthalmologic Manifestations of Wolfram Syndrome: Report of 14 Cases

Next generation sequencing identifies a pathogenic mutation of WFS1 gene in a Moroccan family with Wolfram syndrome: a case report

The Impact of Mutations in Wolframin on Psychiatric Disorders

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