Werdnig-hoffmann Disease
Disease Details
Family Health Simplified
- Description
- Werdnig-Hoffmann disease, also known as spinal muscular atrophy type 1, is a severe genetic disorder characterized by the degeneration of motor neurons, leading to muscle weakness and atrophy that typically begins in infancy.
- Type
- Werdnig-Hoffmann disease is also known as Spinal Muscular Atrophy Type 1 (SMA Type 1). It is an autosomal recessive genetic disorder. This means that an affected individual must inherit two copies of the defective gene, one from each parent. The gene involved is the SMN1 gene, which is responsible for producing a protein essential for the survival of motor neurons.
- Signs And Symptoms
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The symptoms vary depending on the SMA type, the stage of the disease as well as individual factors. Signs and symptoms below are most common in the severe SMA type 0/I:
Areflexia, particularly in extremities
Overall muscle weakness, poor muscle tone, limpness or a tendency to flop
Difficulty achieving developmental milestones, difficulty sitting/standing/walking
In small children: adopting of a frog-leg position when sitting (hips abducted and knees flexed)
Loss of strength of the respiratory muscles: weak cough, weak cry (infants), accumulation of secretions in the lungs or throat, respiratory distress
Bell-shaped torso (caused by using only abdominal muscles for respiration) in severe SMA type
Fasciculations (twitching) of the tongue
Difficulty sucking or swallowing, poor feeding - Prognosis
- In the absence of pharmacological treatment, people with SMA tend to deteriorate over time. Recently, survival has increased in severe SMA patients with aggressive and proactive supportive respiratory and nutritional support.If left untreated, the majority of children diagnosed with SMA type 0 and 1 do not reach the age of 4, recurrent respiratory problems being the primary cause of death. With proper care, milder SMA type I cases (which account for approx. 10% of all SMA1 cases) live into adulthood. Long-term survival in SMA type I is not sufficiently evidenced; however, as of 2007 advances in respiratory support seem to have brought down mortality.In untreated SMA type II, the course of the disease is slower to progress and life expectancy is less than the healthy population. Death before the age of 20 is frequent, although many people with SMA live to become parents and grandparents. SMA type III has normal or near-normal life expectancy if standards of care are followed. Type IV, adult-onset SMA usually means only mobility impairment and does not affect life expectancy.
- Onset
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA Type 1), typically has an onset in infancy, usually within the first six months of life. It is characterized by severe muscle weakness and poor muscle tone.
- Prevalence
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy type 1 (SMA1), has a prevalence of approximately 1 in 10,000 live births.
- Epidemiology
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy type 1 (SMA type 1), is a genetic neuromuscular disorder.
Epidemiology:
- The incidence of Werdnig-Hoffmann disease is approximately 1 in 10,000 live births.
- It is the most severe form of spinal muscular atrophy, usually evident before 6 months of age.
- The disease is caused by mutations in the SMN1 gene, which follows an autosomal recessive inheritance pattern.
- Carrier frequency is roughly 1 in 40 to 1 in 60 in the general population.
Note: I am not familiar with the term "nan" in this context, so I cannot provide information relevant to that. If you meant a different aspect or have a specific question, please clarify. - Intractability
- Yes, Werdnig-Hoffmann disease, also known as spinal muscular atrophy type 1 (SMA1), is generally considered intractable. It is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy caused by the degeneration of motor neurons in the spinal cord. While recent advances in genetic therapies, such as nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and risdiplam (Evrysdi), have improved outcomes and management, the disease remains a significant and often life-limiting condition.
- Disease Severity
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA Type 1), is a severe genetic disorder. It presents with muscle weakness and atrophy, typically evident within the first 6 months of life. The severity is high, leading to significant motor function impairment and often affecting respiratory muscles, which can result in breathing difficulties and potentially life-threatening complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:13137
- Pathophysiology
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA Type 1), involves the progressive degeneration of alpha motor neurons in the anterior horn of the spinal cord. This degeneration leads to muscle atrophy and weakness, particularly affecting the proximal muscles more severely than the distal muscles. The disease is caused by mutations in the SMN1 (Survival Motor Neuron 1) gene, which results in insufficient production of the SMN protein critical for motor neuron survival and function. Elevated nan levels, associated with a diagnostic biomarker, are sometimes observed but are not the direct pathophysiological mechanism of the disease.
- Carrier Status
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA Type 1), is an autosomal recessive disorder. Carrier status means that an individual carries one copy of the mutated gene but does not typically show symptoms of the disease. Each parent of an affected individual is usually a carrier. When two carriers have a child, there is a 25% chance that the child will have the disease, a 50% chance the child will also be a carrier, and a 25% chance the child will not inherit the mutated gene at all.
- Mechanism
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA-1), is a severe neuromuscular disorder.
Mechanism:
Werdnig-Hoffmann disease primarily affects motor neurons in the spinal cord. It leads to the degeneration and loss of these motor neurons, which results in muscle weakness and atrophy. Infants with this condition typically show symptoms such as hypotonia (reduced muscle tone), muscle weakness, and diminished deep tendon reflexes.
Molecular Mechanisms:
The disease is caused by mutations in the SMN1 (Survival Motor Neuron 1) gene located on chromosome 5q13. This gene is crucial for the production of the SMN protein, essential for the maintenance and survival of motor neurons. In most cases, patients have deletions or mutations in the SMN1 gene that result in insufficient levels of functional SMN protein. A related gene, SMN2, can partially compensate for the loss of SMN1, but it produces a truncated, less efficient version of the SMN protein. The number of copies of the SMN2 gene can influence the severity of the disease; more copies generally correlate with a milder phenotype.
The deficiency in SMN protein disrupts various cellular processes, including RNA splicing, intracellular transport, and stress response, ultimately leading to motor neuron apoptosis and the clinical manifestations of the disease. - Treatment
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA1), is a genetic disorder characterized by severe muscle weakness and atrophy.
**Treatment:**
1. **Supportive Care:** This includes respiratory support (such as non-invasive ventilation), nutritional support (gastrostomy feeding if necessary), and physical therapy to manage symptoms.
2. **Medications:**
- **Nusinersen (Spinraza):** Administered via intrathecal injection, it helps to increase the production of functional SMN protein.
- **Onasemnogene abeparvovec-xioi (Zolgensma):** A one-time gene therapy that delivers a copy of the SMN gene.
- **Risdiplam (Evrysdi):** An oral medication that helps increase SMN protein levels.
3. **Multidisciplinary Approach:** Care from neurologists, pulmonologists, nutritionists, and other specialists to address various aspects of the disease.
**Nan:** There are no specific nanotechnology-based treatments or interventions currently approved for Werdnig-Hoffmann disease. However, research continues in the field of nanomedicine which could potentially offer new therapeutic options in the future. - Compassionate Use Treatment
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA Type 1), is a severe genetic disorder characterized by muscle weakness and atrophy. In terms of compassionate use treatments and experimental therapies:
1. **Compassionate Use Treatments**:
- *Nusinersen (Spinraza)*: This FDA-approved drug can sometimes be provided under compassionate use for patients who may not qualify for clinical trials or other treatments.
- *Onasemnogene abeparvovec (Zolgensma)*: Often used under special access programs for infants, this gene therapy has shown efficacy in some cases of SMA Type 1.
2. **Off-Label or Experimental Treatments**:
- *Risdiplam (Evrysdi)*: Although primarily approved for SMA, its use in specific genetic contexts or patient populations might be considered experimental or off-label.
- *Branaplam*: Originally developed for other purposes, it's being investigated for its potential benefits in SMA.
- *Neuroprotective or muscle-boosting agents*: These are in various stages of clinical trials and can sometimes be used off-label based on physician discretion.
Clinical trials continue to assess the efficacy and safety of these and other emerging treatments. Patients and caregivers should consult with healthcare professionals to explore current options. - Lifestyle Recommendations
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1, is a severe genetic disorder that affects motor neurons, leading to muscle weakness and atrophy. Here are some lifestyle recommendations for managing the condition:
1. **Respiratory Support**: Regular monitoring of respiratory function. Use of non-invasive ventilation or tracheostomy may be required.
2. **Nutrition**: Adequate nutritional support, possibly including the use of feeding tubes if oral intake is insufficient.
3. **Physical Therapy**: Gentle physical therapy to maintain joint mobility and prevent contractures.
4. **Positioning**: Proper positioning to support the spine and prevent scoliosis.
5. **Hydration**: Ensure proper hydration to aid general health and muscle function.
6. **Adaptive Equipment**: Use of specialized equipment like wheelchairs and adjustable beds to improve mobility and comfort.
7. **Infection Prevention**: Vigilant care to prevent respiratory infections, including vaccinations and avoiding exposure to illness.
8. **Regular Medical Follow-up**: Consistent monitoring by a multidisciplinary team including neurologists, pulmonologists, and nutritionists.
These recommendations are not exhaustive and should be tailored to the individual needs of the patient in consultation with healthcare providers. - Medication
- Nusinersen (marketed as Spinraza) is used to treat spinal muscular atrophy. It is an antisense nucleotide that modifies the alternative splicing of the SMN2 gene. It is given directly to the central nervous system using an intrathecal injection. Nusinersen prolongs survival and improves motor function in infants with SMA. It was approved for use in the US in 2016, and for use in the EU in 2017.Onasemnogene abeparvovec (marketed as Zolgensma) is a gene therapy treatment which uses self-complementary adeno-associated virus type 9 (scAAV-9) as a vector to deliver the SMN1 transgene. The therapy was first approved in the US in May 2019 as an intravenous formulation for children below 24 months of age. Approval in the European Union, Japan and other countries followed, albeit often with different approval scopes.Risdiplam (marketed as Evrysdi) is a medication taken by mouth in liquid form. It is a pyridazine derivative that works by increasing the amount of functional survivor motor neuron protein produced by the SMN2 gene through modifying its splicing pattern. Risdiplam aims to increase the amount of SMN protein so that there is enough protein to sustain the peripheral nervous system tissues which are usually the most damaged by SMA. Risdiplam was first approved for medical use in the United States in August 2020 and has since been approved in over 30 countries.
- Repurposable Drugs
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Werdnig-Hoffmann disease, also known as spinal muscular atrophy type 1 (SMA1), primarily affects infants and leads to severe muscle weakness and atrophy. While there is no cure, some drugs originally developed for other purposes have shown potential benefits:
1. **Nusinersen (Spinraza)**: Initially developed for SMA, it has shown to improve motor function in various types of SMA including SMA1.
2. **Risdiplam (Evrysdi)**: This drug modifies the SMN2 gene to increase the production of functional SMN protein.
3. **Onasemnogene abeparvovec-xioi (Zolgensma)**: Although a gene therapy specifically designed for SMA, it can be considered as a targeted treatment rather than a repurposed drug.
Research is ongoing to identify other repurposable drugs that may benefit SMA1 patients. - Metabolites
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Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy Type 1 (SMA1), primarily affects motor neurons but does not have well-defined specific metabolites associated with it. The disease is characterized by the degeneration of motor neurons in the spinal cord due to mutations in the SMN1 gene, leading to muscle weakness and atrophy.
The abbreviation "nan" typically stands for "not a number" and does not directly relate to a specific aspect of Werdnig-Hoffmann disease. If you meant something different by "nan," please provide additional context. - Nutraceuticals
- Werdnig-Hoffmann disease, also known as Spinal Muscular Atrophy (SMA) Type 1, is a genetic disorder affecting motor neurons. While nutraceuticals (food-derived products with potential health benefits) may offer supportive care, they do not cure or halt the progression of the disease. Common examples include antioxidant supplements, omega-3 fatty acids, and vitamins like vitamin D, which might help in maintaining overall health and potentially support muscle function to some extent. However, the primary focus for SMA Type 1 is usually on medical treatments, supportive therapies, and nutritional support under professional guidance.
- Peptides
- Werdnig-Hoffmann disease, also known as spinal muscular atrophy type 1 (SMA1), is a genetic disorder characterized by progressive muscle weakness and atrophy. It is caused by mutations in the SMN1 gene, which is crucial for the production of survival motor neuron (SMN) protein. The disease primarily affects motor neurons in the spinal cord, leading to severe physical impairments. While peptides and nanotechnology are areas of active research in many fields, current treatments for SMA1 often focus on gene therapy, antisense oligonucleotides, and supportive care, rather than specific peptide-based or nanotechnology-based therapies.