Introduction
Wolfram syndrome is a low condition. It is also known as diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) syndrome. Dr. Don J. Wolfram first described Wolfram syndrome in 1938. Diabetes and vision issues are the first symptoms of Wolfram syndrome, which typically appear before age 15. Wolfram syndrome impacts the central nervous system (brain stem), resulting in reduced brain function and early death.
What Is Wolfram Syndrome?
Wolfram syndrome (WFS) is a rare inherited condition. It is characterized by hearing problems, early-onset insulin-dependent diabetes mellitus, and vision problems. WFS can be associated with a variety of other neurological symptoms as well as other systemic findings.
Wolfram syndrome is classified based on gene mutation into two types.
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Type 1 Wolfram Syndrome - It occurs due to WFS1 gene mutations.
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Type 2 Wolfram Syndrome - Due to conversion of CISD2 gene.
How Common Is Wolfram Syndrome?
Wolfram syndrome (WFS) is a rare disease with wide prevalence estimates ranging from 1 in 770,000 in the United Kingdom to 1 in 100,000 in the North American population. Type 1 Wolfram syndrome affects approximately one in 500,000 people globally.
What Are the Causes of Wolfram Syndrome?
Mitochondrial dysfunction was earlier considered the cause of Wolfram syndrome. However, recent studies established endoplasmic reticulum dysfunction as the cause of Wolfram syndrome. More than 90 percent of type 1 Wolfram syndrome cases are caused by variations (mutations) in the WFS1 gene. WFS1 gene mutations result in the production of wolframin proteins with altered and reduced function. This will result in modified calcium levels within cells, and the endoplasmic reticulum will fail to function correctly. Wolfram syndrome type 2 has been linked to a specific CISD2 gene variation.
What Are the Symptoms of Wolfram Syndrome?
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Neonatal Diabetes Mellitus - Diabetes mellitus will likely develop in every person with Wolfram syndrome. In this condition, the body usually has trouble absorbing glucose (sugar) from food. When the body fails to produce adequate levels of insulin or the cells do not respond properly, it can result in imbalanced blood sugar levels. Even though diabetes related to Wolfram syndrome is not an autoimmune condition, it is similar to type 1 diabetes. Frequent urination, blurred vision, increased thirst, and unexplained weight loss are some signs and symptoms of diabetes.
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Optic Atrophy - At some point, optic atrophy affects everyone with Wolfram syndrome. The optic nerves involve the transmission of signals from the eyes to the brain. Optic atrophy usually occurs due to the degeneration of the optic nerve. Symptoms include blurred vision and reduced peripheral vision.
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Renal Problems - Two-thirds of Wolfram syndrome patients have renal problems. This can result in bedwetting, frequent passing of urine, and a loss of bladder control. Some patients may have recurrent urinary tract infections and incomplete bladder emptying.
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Deafness - Approximately two-thirds of people with Wolfram syndrome will have hearing loss. Rephrased: Damage to the inner ear is the underlying cause of sensorineural hearing loss. The affected individuals may have difficulty hearing high-pitched sounds or hearing in a crowded room. As a result, one in every four Wolfram syndrome patients requires a hearing aid.
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Neurological Problems - One-fourth of those with Wolfram syndrome may experience neurological issues. It includes problems with coordination, loss of balance, loss of smell and taste, sudden muscle jerks, breathing problems, central sleep apnea, and headaches.
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Fatigue - Wolfram syndrome patients' physical stamina declines over time. They will require more sleep as their condition worsens.
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Hormonal Issues - Affected individuals may have hormonal disorders. It includes low sex drive, hypopituitarism, delayed onset of menstruation, and growth delays.
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Psychiatric Conditions - Aggressive behavior, panic attacks, depression, and anxiety are some psychiatric conditions seen in Wolfram syndrome patients.
How Is Wolfram Syndrome Diagnosed?
Wolfram syndrome can be challenging to diagnose. Diagnosis of Wolfram syndrome is usually made after observing several symptoms. If the doctor suspects Wolfram syndrome, genetic testing will be suggested. This test can confirm the diagnosis by detecting mutations in the WFS1 and WFS2 (CISD2) genes.
Molecular genetic testing can confirm the disease, provide genetic counseling, and screen high-risk, asymptomatic individuals with a significant family history. Identification of carrier heterozygotes with WFS1 mutations enables psychiatric monitoring, as these individuals are 26 times more likely than noncarriers to require psychiatric hospitalization.
In WFS1 patients, MRI (magnetic resonance imaging) findings can reveal generalized atrophy of the hypothalamus, brain, cerebellum, brainstem, and cerebral cortex. Other findings include the shrinkage of the optic nerves, tracts, chiasm, and a reduction in posterior pituitary signal.
How Is Wolfram Syndrome Treated?
Wolfram syndrome has no cure, but some of its symptoms can be treated. These include:
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Insulin for diabetes.
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Antibiotics for UTIs (urinary tract infections).
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Desmopressin for diabetes insipidus.
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Use of hearing aids for Wolfram syndrome-associated hearing loss.
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Supportive aids like magnifying glasses for visual loss.
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Optic nerve atrophy, resulting in loss of visual acuity, is the most significant symptom of Wolfram syndrome and the primary cause of concern for patients. A yearly eye checkup, with vision testing, visual acuity, visual field, fundoscopy, and an optical coherence tomography (OCT) scan, is strongly advised.
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In some people, headaches associated with Wolfram syndrome can be managed with Carbamazepine or Amitriptyline.
Up to 60 percent of WFS patients show early mortality (below 36). Central respiratory failure, dysphagia, autonomic dysfunction, or aspiration pneumonia are the most frequent reasons for death. Due to the complexity and wide range of possible manifestations across organ systems, multidisciplinary care is required for Wolfram syndrome patients.
What Is the Prognosis of Wolfram Syndrome?
Recent research advances have resulted in the development of treatments to slow the progression of Wolfram syndrome. Leading treatment approaches like regenerative medicine, drugs to decrease cell damage, and gene therapy to replace or repair mutated WFS1 and two genes can increase the prognosis of Wolfram syndrome.
Conclusion
Wolfram syndrome (WFS) is a rare genetic condition. Typical symptoms of Wolfram syndrome include neurological abnormalities, childhood-onset diabetes mellitus, deafness, optic atrophy, diabetes insipidus, and other conditions. DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) is another name for the syndrome. Mutations in the WFS-1 gene are the main reason for Wolfram syndrome. There is no specific treatment for Wolfram syndrome, and the goal of treatment of Wolfram syndrome is to treat associated symptoms.
