Troyer Syndrome
Disease Details
Family Health Simplified
- Description
- Troyer syndrome is a rare hereditary spastic paraplegia characterized by progressive spasticity and weakness of the lower limbs, along with developmental and cognitive impairments.
- Type
- Troyer syndrome is a type of hereditary spastic paraplegia. It is transmitted via autosomal recessive inheritance.
- Signs And Symptoms
-
Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia.
Individuals with HSP can experience extreme fatigue associated with central nervous system and neuromuscular disorders, which can be disabling. Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices. Disability has been described as progressing more rapidly in adult onset forms.More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles.
In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, intellectual disability, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom.This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, intellectual disability (with spasticity), or leukodystrophy. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups. - Prognosis
- Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling whilst others leave people able to do most ordinary activities to an ordinary extent without needing adjustments. The majority of individuals with HSP have a normal life expectancy.
- Onset
- The onset of Troyer syndrome, a rare hereditary spastic paraplegia, typically occurs in early childhood. Manifestations often appear within the first two years of life.
- Prevalence
- Troyer syndrome is an extremely rare hereditary spastic paraplegia. The exact prevalence is not well-documented due to its rarity, but it is known to be more prevalent in the Amish population in the United States. No accurate prevalence data (nan) is available for the general population.
- Epidemiology
- Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population – a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population.
- Intractability
- Troyer syndrome is considered a form of hereditary spastic paraplegia (HSP) and is typically a chronic condition for which there is currently no cure. The management of Troyer syndrome focuses on alleviating symptoms and improving quality of life through physical therapy, medications for spasticity, and other supportive treatments. Therefore, it can be described as intractable in the sense that it is not curable and requires ongoing management.
- Disease Severity
- Troyer syndrome is a type of hereditary spastic paraplegia. The severity can vary among individuals but typically includes progressive weakness and spasticity in the lower limbs, along with other possible symptoms like dysarthria, developmental delays, and cognitive impairment. The condition is generally progressive, leading to increasing disability over time.
- Healthcare Professionals
- Disease Ontology ID - DOID:0050886
- Pathophysiology
- The major feature of HSP is a length-dependent axonal degeneration. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent. Neuronal cell bodies of degenerating axons are preserved and there is no evidence of primary demyelination. Loss of anterior horn cells of the spinal cord are observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are not directly affected.HSP affects several pathways in motor neurons. Many genes were identified and linked to HSP. It remains a challenge to accurately define the key players in each of the affected pathways, mainly because many genes have multiple functions and are involved in more than one pathway.
- Carrier Status
- Troyer syndrome is an autosomal recessive neurodegenerative disorder. Carrier status means a person has one copy of the mutated gene but does not typically show symptoms. They can pass the gene to their offspring, who may develop the disease if they inherit two copies of the mutated gene—one from each parent. "Nan" typically stands for not applicable here.
- Mechanism
-
Troyer syndrome is a form of hereditary spastic paraplegia (HSP) caused by mutations in the SPART gene, which encodes the spartin protein. The principal mechanism involves the disruption of normal spartin function, which is critical for proper cellular processes including endosomal trafficking, mitochondrial function, and lipid droplet formation.
Molecular mechanisms:
1. **Endosomal Trafficking**: Spartin is involved in endosomal sorting and trafficking. Mutations in SPART can impair these processes, leading to defective recycling of receptors and other cargo that are crucial for cellular communication and nutrient uptake.
2. **Mitochondrial Dysfunction**: Spartin has a role in maintaining mitochondrial morphology and function. Mutations can disrupt mitochondrial dynamics, resulting in energy production deficits and increased oxidative stress.
3. **Lipid Droplet Formation**: Spartin is also involved in the regulation of lipid droplets, which are important for lipid storage and metabolism. Disruption in spartin function may lead to abnormal lipid metabolism, contributing to cellular dysfunction.
These disruptions ultimately manifest as the clinical features of Troyer syndrome, including spasticity, weakness, and other neurological symptoms. - Treatment
-
No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include:
Baclofen – a voluntary muscle relaxant to relax muscles and reduce tone. This can be administered orally or intrathecally. (Studies in HSP )
Tizanidine – to treat nocturnal or intermittent spasms (studies available )
Diazepam and clonazepam – to decrease intensity of spasms
Oxybutynin chloride – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
Tolterodine tartrate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
Cro System – to reduce muscle overactivity (existing studies for spasticity )
Botulinum toxin – to reduce muscle overactivity (existing studies for HSP patients)
Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression
Physical therapy – to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores. - Compassionate Use Treatment
-
Troyer syndrome, or SPG20, is a rare form of hereditary spastic paraplegia. Currently, there is no cure or well-established treatment specifically approved for this condition. However, some off-label or experimental approaches might be considered under compassionate use. These can include:
1. **Baclofen, Tizanidine, or Botulinum Toxin**: These muscle relaxants can be used off-label to manage spasticity.
2. **Physical Therapy**: Often recommended to maintain mobility and muscle strength.
3. **Occupational Therapy**: Helps individuals with daily activities and improve their quality of life.
4. **Speech Therapy**: May be beneficial, given that speech difficulties can be part of the syndrome's symptomatology.
5. **Genetic Therapies**: Experimental treatments aimed at addressing the underlying genetic cause, though these are still in the research phase.
Individuals considering these options should consult with their healthcare providers to evaluate the potential benefits and risks. - Lifestyle Recommendations
-
Troyer syndrome, also known as hereditary spastic paraplegia type 20 (SPG20), is a genetic disorder characterized by progressive weakness and spasticity of the lower limbs along with other symptoms like developmental delays, speech difficulties, and distal muscle wasting.
### Lifestyle Recommendations:
1. **Physical Therapy:**
- Regular physical therapy can help maintain muscle strength and flexibility.
- Stretching exercises can prevent contractures and improve mobility.
2. **Occupational Therapy:**
- Assistive devices and adaptive techniques may help with daily activities.
- Training in the use of mobility aids such as walkers or wheelchairs.
3. **Speech Therapy:**
- To address speech and communication difficulties, regular sessions with a speech therapist may be beneficial.
4. **Nutritional Management:**
- A balanced diet to maintain overall health and avoid additional complications.
- In cases of difficulty swallowing, a nutritionist may recommend appropriate dietary modifications.
5. **Genetic Counseling:**
- For families affected by Troyer syndrome, genetic counseling can provide information on inheritance patterns and family planning options.
6. **Social Support:**
- Engaging with support groups for individuals with hereditary spastic paraplegias.
- Mental health support to address any psychological or emotional challenges.
7. **Regular Medical Follow-Up:**
- Continuous monitoring by a neurologist or a specialist familiar with hereditary spastic paraplegias is crucial.
- Early intervention for managing symptoms and complications.
Implementing these lifestyle recommendations can help improve quality of life and manage the symptoms associated with Troyer syndrome. - Medication
-
Troyer syndrome is a type of hereditary spastic paraplegia (HSP) caused by mutations in the SPG20 gene. Treatment primarily focuses on managing symptoms, as there is no cure. Medications may include:
- Muscle relaxants like baclofen or tizanidine for spasticity.
- Anticholinergic agents for bladder control issues.
- Antidepressants or anticonvulsants for managing neuropathic pain.
Physical therapy, occupational therapy, and assistive devices also play critical roles in managing the condition. Always consult a healthcare provider for a personalized treatment plan. - Repurposable Drugs
- Troyer syndrome, a rare hereditary spastic paraplegia, currently lacks specific treatments. Research is ongoing into repurposable drugs to manage symptoms. One candidate for repurposing is baclofen, which is a muscle relaxant commonly used for spasticity in other conditions. Another is botulinum toxin, which can help reduce muscle stiffness and spasms. Additionally, potential treatments focusing on neuroinflammation, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may also provide symptomatic relief. Clinical trials and further studies are necessary to validate their efficacy specifically for Troyer syndrome.
- Metabolites
- Troyer syndrome is a type of hereditary spastic paraplegia. While specific metabolic profiles for Troyer syndrome are not widely documented, it is primarily characterized by the mutation in the SPG20 gene, leading to the dysfunction of the spartin protein. Research is still ongoing to fully understand the disease's metabolic aspects.
- Nutraceuticals
- There is limited specific information available regarding the use of nutraceuticals for Troyer syndrome, a rare hereditary spastic paraplegia. Nutraceuticals are food-derived products with potential health benefits, but their efficacy for Troyer syndrome is not well-documented. Consulting with a healthcare provider is advisable for tailored nutritional and medical advice for managing this condition.
- Peptides
-
Troyer syndrome is a rare hereditary spastic paraplegia characterized by progressive muscle weakness and stiffness (spasticity), especially in the lower limbs. It's caused by mutations in the SPG20 gene.
If your query involves treatments involving peptides or the use of nanoparticles (nan), as of the most recent knowledge, there are no specific peptide-based or nanoparticle-based therapies widely recognized or approved for Troyer syndrome. Current management typically focuses on symptomatic treatment, including physical therapy, medications to reduce spasticity, and supportive care. Advances in biotechnology and molecular medicine may eventually lead to new treatment options, but they are not established at this time.