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Autosomal Recessive Distal Spinal Muscular Atrophy 1

Disease Details

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Description: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is a genetic disorder characterized by progressive muscle weakness and atrophy, primarily affecting the distal muscles of the limbs, due to degeneration of motor neurons in the spinal cord.

One-sentence description: Autosomal recessive distal spinal muscular atrophy 1 is a genetic disorder causing progressive muscle weakness and atrophy in the limbs due to spinal motor neuron degeneration.
Type: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is characterized by an autosomal recessive type of genetic transmission. This means that an individual must inherit two copies of the defective gene, one from each parent, to develop the condition.
Signs And Symptoms: Usually, the first respiratory symptoms are shortness of breath (dyspnea) and paradoxical respirations which then escalate within the first few months of life to diaphragmatic paralysis. The symptoms of diaphragmatic paralysis come on very rapidly and without warning, and the patient is often rushed to a hospital where they are placed on a ventilator for respiratory support. Due to the severe nature of diaphragmatic paralysis, the patient eventually needs continuous ventilation support to survive. Continuous ventilation, however, may in itself cause damage to the anatomy of the lungs.In addition to diaphragmatic paralysis, other issues may arise: as the name suggests, the distal limbs are most affected with symptoms of weakness, restricting mobility due to (near-)paralysis of the distal limbs as well as the head and neck. Also, dysfunction of the peripheral nerves and the autonomic nervous system may occur. Due to these dysfunctions, the patients have been shown to suffer from excessive sweating and irregular heartbeat. The deep tendon reflex is also lost in patients with DSMA1.Uterine growth retardation and poor foetal movement have been observed in severe DSMA1 cases.
Prognosis: DSMA1 is usually fatal in late infancy or early childhood. The child suffers a progressive degradation of the respiratory system until respiratory failure. There is no consensus on the life expectancy in DSMA1 despite a number of studies being conducted. A small number of patients survive past two years of age but they lack signs of diaphragmatic paralysis or their breathing is dependent on a ventilation system.
Onset: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) typically has an onset in infancy or early childhood.
Prevalence: The prevalence of autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is not well-documented and is generally considered to be very rare, with only a few cases reported in medical literature.
Epidemiology: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is a rare genetic disorder. As with many rare genetic conditions, precise epidemiological data is often limited. Its prevalence is not well-defined, but it is known to be rare. The disease is inherited in an autosomal recessive manner, which means that both copies of the gene in each cell have mutations, and typically, each parent of an individual with the condition carries one copy of the mutated gene but does not show symptoms.
Intractability: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is not intractable, meaning it is not beyond management or control. However, it is a chronic condition with no known cure. Treatment typically focuses on managing symptoms and improving quality of life, often requiring multidisciplinary care.
Disease Severity: Autosomal recessive distal spinal muscular atrophy type 1 (DSMA1) generally presents with early onset of muscle weakness and wasting, predominantly affecting the distal muscles of the limbs. The severity of the disease can vary, but it often leads to significant disability. Some individuals may retain the ability to walk, while others might require mobility aids or become wheelchair-dependent.
Healthcare Professionals: Disease Ontology ID - DOID:0111064
Pathophysiology: The pathology underlying the observable characteristics of DSMA1 is cell body degeneration of motor nerves. Specifically, the anterior horn α-motorneurons degenerate within the first six months of life leading to a variety of symptoms. Muscle deterioration increases at around 1–2 years of age, resulting in reduced motor function. The most severely affected muscles include facial muscles and the tongue (which may develop a twitch due to hypoglossal nerve paralysis). Reduced pain sensation and excessive sweating are sometimes observed. Non-ambulant patients may develop pressure ulcers, severe constipation, urinary incontinence, and (rarely) reflux nephropathy in the advanced stages of the disease.
Carrier Status: Autosomal recessive distal spinal muscular atrophy type 1 (DSMA1) is a genetic disorder inherited in an autosomal recessive manner. In this type of inheritance, a person must have two copies of the mutated gene, one from each parent, to exhibit symptoms of the disorder. If a person has only one copy of the mutated gene, they are considered a carrier. Carriers typically do not show symptoms of the disease but can pass the mutated gene to their offspring. If two carriers have a child, there is a 25% chance the child will have the disorder, a 50% chance the child will be a carrier, and a 25% chance the child will have two normal copies of the gene.
Mechanism: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is a genetic disorder characterized by muscle weakness and atrophy primarily affecting the distal muscles, which are the muscles farthest from the center of the body, such as those in the hands and feet.

Mechanism:
DSMA1, like other forms of spinal muscular atrophy (SMA), is caused by the degeneration of motor neurons in the anterior horn of the spinal cord. This neurodegeneration leads to muscle wasting and weakness because motor neurons are essential for muscle contraction.

Molecular Mechanisms:
DSMA1 is typically associated with mutations in the gene encoding the protein "IGHMBP2" (immunoglobulin mu-binding protein 2). IGHMBP2 is involved in RNA processing and translation. Mutations in IGHMBP2 lead to defective or insufficient protein production, disrupting normal motor neuron function and survival. The precise molecular mechanisms are still under investigation, but it is believed that the dysfunction in RNA processing critically impairs motor neurons, causing their degeneration and the consequent muscle atrophy.
Treatment: There is no known cure to DSMA1, and care is primarily supportive. Patients require respiratory support which may include non-invasive ventilation or tracheotomy. The child may also undergo additional immunisations and offered antibiotics to prevent respiratory infections. Maintaining a healthy weight is also important. Patients are at risk of undernutrition and weight loss because of the increased energy spent for breathing. Physical and occupational therapy for the child can be very effective in maintaining muscle strength.There is no published practice standard for the care in DSMA1, even though the Spinal Muscular Atrophy Standard of Care Committee has been trying to come to a consensus on the care standards for DSMA1 patients. The discrepancies in the practitioners’ knowledge, family resources, and differences in patient's culture and/or residency have played a part in the outcome of the patient.
Compassionate Use Treatment: Autosomal recessive distal spinal muscular atrophy type 1 (DSMA1) is a genetic disorder characterized by progressive muscle weakness and atrophy, primarily affecting the distal muscles of the limbs. There are no specific treatments approved for DSMA1, but compassionate use, off-label, or experimental treatments may provide some relief.

1. **Compassionate Use Treatment**:
- **Nusinersen (Spinraza)**: Originally approved for spinal muscular atrophy (SMA), its use in DSMA1 might be considered on a compassionate basis. It requires intrathecal administration.
- **Gene Therapy**: Investigational gene therapy approaches targeting genetic causes of DSMA1 might be available under compassionate use programs.

2. **Off-Label Treatments**:
- **Riluzole**: Commonly used for amyotrophic lateral sclerosis (ALS), this drug might be considered off-label to slow disease progression.
- **Valproic Acid**: Sometimes used off-label for other types of SMA, although efficacy is uncertain.

3. **Experimental Treatments**:
- **Gene Therapy Trials**: Ongoing clinical trials may be exploring the efficacy of gene therapies aimed at correcting the genetic defect underlying DSMA1.
- **Stem Cell Therapy**: Experimental approaches involving stem cell transplantation are being researched to potentially regenerate affected neurons.
- **Small Molecule Drugs**: Investigational drugs targeting specific molecular pathways involved in neuron survival and muscle function are in development.

Patients or caregivers should consult with healthcare professionals to explore these options, as eligibility for compassionate use or clinical trials varies and may involve specific criteria and regulatory approvals.
Lifestyle Recommendations: For individuals with autosomal recessive distal spinal muscular atrophy 1, lifestyle recommendations typically include:

1. **Physical Therapy**: Regular exercises to maintain muscle strength and flexibility. A physical therapist can design a program tailored to the individual's needs.
2. **Occupational Therapy**: Techniques to enhance the ability to perform daily activities. This might include adaptive devices.
3. **Assistive Devices**: Use of braces, walkers, or wheelchairs as needed to aid mobility.
4. **Nutrition**: A well-balanced diet to maintain optimal health and energy levels. Consulting with a nutritionist may be beneficial.
5. **Respiratory Care**: Regular monitoring and exercises to maintain lung function, as respiratory muscles can be affected.
6. **Hydrotherapy**: Water-based exercises can help with muscle relaxation and movement flexibility without putting strain on the body.
7. **Pain Management**: Techniques such as massage, heat therapy, or medication as prescribed by a healthcare provider.
8. **Emotional Support**: Counseling or support groups to help with mental and emotional well-being.

It is important for individuals to work closely with their healthcare team to develop a personalized plan that addresses their specific needs and abilities.
Medication: For autosomal recessive distal spinal muscular atrophy 1 (DSMA1), there is currently no specific medication approved to cure or directly treat the condition. Management primarily focuses on symptomatic relief and supportive care, including physical therapy, assistive devices for mobility, respiratory support if needed, and regular monitoring by healthcare professionals. Genetic counseling is also recommended for affected families.
Repurposable Drugs: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is a genetic disorder characterized by muscle weakness and atrophy, primarily affecting distal muscles. Currently, there are no specific repurposable drugs identified for the treatment of DSMA1. Management generally focuses on supportive care, including physical therapy and assistive devices to improve quality of life. Clinical trials and research are ongoing to explore potential therapeutic options.
Metabolites: Autosomal recessive distal spinal muscular atrophy 1 (DSMA1) is primarily a genetic disorder affecting motor neurons, leading to muscle weakness and atrophy. There isn't a specific metabolic pathway or known metabolites directly associated with DSMA1 because it is primarily linked to genetic mutations rather than metabolic dysregulation. The focus of the disorder is on the genetic mutation in the IGHMBP2 gene leading to the pathology. Therefore, there are no distinct metabolites that have been identified as markers or involved in DSMA1.
Nutraceuticals: As of the current available research, there are no specific nutraceuticals identified for the treatment or management of autosomal recessive distal spinal muscular atrophy type 1. Nutraceuticals, which are products derived from food sources with extra health benefits, are not a standard treatment for this genetic disorder. Management usually involves supportive care, physical therapy, and possibly the use of mobility aids. It is important to consult with healthcare professionals for tailored management strategies.
Peptides: Autosomal Recessive Distal Spinal Muscular Atrophy 1 (DSMA1), also known as distal hereditary motor neuropathy type 3 (HMN3), is primarily a genetic disorder characterized by muscle weakness and atrophy. The term "peptides" in the context of DSMA1 might refer to potential biomarkers or therapeutic agents under research; however, specific peptides directly involved in DSMA1 are not well-established in literature. Its underlying cause is often linked to mutations in the IGHMBP2 gene. More comprehensive treatments or research efforts may eventually identify particular peptides of interest for diagnosis or therapy.