The SPG7 gene holds the instructions for creating paraplegin, a protein that operates within the energy-producing centers of our cells, known as mitochondria. This protein is important for the health and function of nerve cells, which have high energy demands. Proper functioning of paraplegin ensures these cellular powerhouses can support the nervous system.
The Function of the SPG7 Gene
The SPG7 gene’s primary role is to produce the protein paraplegin. Paraplegin is a component of a larger protein machine called the m-AAA protease, located in the inner membrane of mitochondria. This complex acts as a quality control manager for the cell’s powerhouses. It identifies, removes, and breaks down damaged or misfolded proteins inside the mitochondria, which prevents their accumulation and maintains mitochondrial efficiency.
This quality control function ensures that mitochondria can continue to generate energy effectively. The m-AAA protease also helps assemble ribosomes, the cellular machinery responsible for building new proteins within the mitochondria. By clearing out old components and assisting in the creation of new ones, the complex helps sustain the high energy output required by neurons.
Hereditary Spastic Paraplegia Type 7
When the SPG7 gene contains mutations, it can lead to a condition known as Hereditary Spastic Paraplegia Type 7 (SPG7-HSP). HSPs are a group of inherited neurological disorders. In SPG7-HSP, defects in the paraplegin protein disrupt its function within the mitochondria. The resulting mitochondrial dysfunction is a primary cause of the nerve cell degeneration seen in the condition.
SPG7-HSP is inherited in an autosomal recessive pattern. This means an individual must inherit one mutated copy of the SPG7 gene from each parent to develop the condition. A person with only one mutated copy is a carrier who does not show symptoms but can pass the gene mutation to their children. This pattern explains why the condition may appear in a family with no prior history.
Clinical Manifestations and Symptoms
The main symptom of SPG7-HSP is progressive spasticity, a feeling of muscle stiffness and tightness, primarily in the lower limbs. This is often accompanied by weakness in the same muscles, leading to difficulties with walking and balance. The onset of symptoms can occur anytime from childhood to late adulthood, and the rate of progression varies significantly among individuals.
SPG7-HSP is often called a “complicated” form of HSP because it can involve a wider range of neurological symptoms beyond leg spasticity. Many individuals experience ataxia, a lack of voluntary coordination of muscle movements that can affect gait, speech, and eye movements. Dysarthria, or difficulty speaking, may also occur.
Other potential symptoms can include:
- Vision problems due to optic atrophy, where the optic nerve degenerates over time.
- Issues with bladder control.
- Sensory changes in the limbs.
- Mild cognitive changes.
The specific combination and severity of these symptoms differ from person to person.
The Diagnostic Process
The diagnostic process for SPG7-HSP begins with a clinical evaluation by a neurologist. This involves a detailed personal and family medical history and a comprehensive neurological examination. The exam assesses muscle strength, tone, reflexes, coordination, balance, and sensation to characterize the symptoms.
To rule out other conditions with similar symptoms, such as multiple sclerosis, neuroimaging is often used. A magnetic resonance imaging (MRI) scan of the brain and spinal cord is standard. While the MRI may be normal in early stages, it can sometimes reveal cerebellar atrophy (shrinkage of the part of the brain that controls coordination), a common finding in SPG7-HSP.
A definitive diagnosis is achieved through molecular genetic testing. This involves a blood test to analyze DNA for mutations in the SPG7 gene. Because the condition is autosomal recessive, the test must identify two mutated copies of the gene to confirm the diagnosis. Genetic counseling is often recommended to help families understand the results.
Therapeutic and Management Strategies
There is no cure for SPG7-HSP, so treatment focuses on managing symptoms to enhance mobility and maintain quality of life. This is achieved through a multidisciplinary approach, involving a team of healthcare professionals. The team often includes a neurologist, physical therapist, occupational therapist, and other specialists as needed.
Physical therapy is a component of management, with exercises designed to stretch spastic muscles, maintain range of motion, and strengthen muscles. Therapists may also recommend assistive devices such as:
- Ankle-foot orthoses
- Canes
- Walkers
- Wheelchairs
These aids can help conserve energy and improve stability.
Medications are often prescribed to help manage spasticity. Oral medications like baclofen and tizanidine are commonly used to reduce muscle stiffness and spasms. For some individuals, injections of botulinum toxin into specific muscles can provide temporary relief.
Occupational therapy helps individuals adapt their homes and daily routines to accommodate physical limitations. This ensures they can continue to participate in meaningful activities safely and effectively.