About spinal muscular atrophy type i

What is spinal muscular atrophy type i?

The spinal muscular atrophies (SMAs), are characterized by degeneration of nerve cells (motor nuclei) within the lowest region of the brain (lower brainstem) and certain motor neurons in the spinal cord (anterior horn cells) leading to muscle weakness of the truncal, and extremity muscles initially, followed by chewing, swallowing and breathing difficulties. Motor neurons are nerve cells that transmit nerve impulses from the spinal cord or brain (central nervous system) to muscle or glandular tissue.

Approximately 80 percent of individuals with SMA fall into the severe category (Werdnig-Hoffman disease or SMA1). Infants with SMA1 experience severe weakness before 6 months of age, and the patient never achieves the ability to sit independently when placed. Muscle weakness, lack of motor development and poor muscle tone are the major clinical manifestations of SMA1. Infants with the gravest prognosis have problems sucking or swallowing. Some show abdominal breathing in the first few months of life. Abdominal breathing is noted when the abdomen protrudes during inspiration. Normally, the chest expands during inspiration as the intercostal muscles (the muscles between the ribs) expand during inspiration. Abdominal breathing occurs when the intercostal muscles are weak and the diaphragm muscle is responsible for inspiration. Movement of the diaphragm (the muscle between the chest and abdomen) expands causing the abdomen to move during the inspiration cycle. Twitching of the tongue is often seen (fasciculations). Cognitive development is normal. Most affected children die before 2 years of age but survival may be dependent on the degree of respiratory function and respiratory support.

The different subtypes, SMA 0-4 are based on the age of onset of symptoms and the course and progression of the disease. SMA represents a continuum or spectrum of disease with a mild end and a severe end. SMA0 patients are extremely weak at birth, require immediate artificial ventilation and will never breathe independently. Werdnig-Hoffman disease, which is also known as spinal muscular atrophy type 1 (SMA1) or acute spinal muscular atrophy, refers to individuals who have symptom onset prior to 6 months of age. SMA 2 patients will show symptoms prior to age 1 year, will sit but never walk. SMA 3 patients (Kugelberg-Welander disease) will show symptoms after age 1, and will walk for a period of time prior to loss of motor abilities. SMA 4 patients will not develop symptoms much before age 10 years.

All the SMAs are inherited as an autosomal recessive trait. Molecular genetic testing has revealed that all types of autosomal recessive SMA are caused by disruptions or errors (mutations) in the SMN1 (survival motor neuron 1) gene on chromosome 5.

What are the causes for spinal muscular atrophy type i?

Mutations in the SMN1 gene cause all types of spinal muscular atrophy described above. The number of copies of the SMN2 gene modifies the severity of the condition and helps determine which type develops.

The SMN1 and SMN2 genes both provide instructions for making a protein called the survival motor neuron (SMN) protein. Normally, most functional SMN protein is produced from the SMN1 gene, with a small amount produced from the SMN2 gene. Several different versions of the SMN protein are produced from the SMN2 gene, but only one version is functional; the other versions are smaller and quickly broken down. The SMN protein is one of a group of proteins called the SMN complex, which is important for the maintenance of motor neurons. Motor neurons transmit signals from the brain and spinal cord that tell skeletal muscles to tense (contract), which allows the body to move.

Most people with spinal muscular atrophy are missing a piece of the SMN1 gene, which impairs SMN protein production. A shortage of SMN protein leads to motor neuron death, and as a result, signals are not transmitted between the brain and muscles. Muscles cannot contract without receiving signals from the brain, so many skeletal muscles become weak and waste away, leading to the signs and symptoms of spinal muscular atrophy.

Typically, people have two copies of the SMN1 gene and one to two copies of the SMN2 gene in each cell. However, the number of copies of the SMN2 gene varies, with some people having up to eight copies. In people with spinal muscular atrophy, having multiple copies of the SMN2 gene is usually associated with less severe features of the condition that develop later in life. The SMN protein produced by the SMN2 genes can help make up for the protein deficiency caused by SMN1 gene mutations. People with spinal muscular atrophy type 0 usually have one copy of the SMN2 gene in each cell, while those with type I generally have one or two copies, those with type II usually have three copies, those with type III have three or four copies, and those with type IV have four or more copies. Other factors, many unknown, also contribute to the variable severity of spinal muscular atrophy.

What are the treatments for spinal muscular atrophy type i?

Curing spinal muscular atrophy I (SMA) is not currently achievable; however, research to identify novel treatments is ongoing.

Treatment and assistance are available to help persons with the disorder manage their symptoms and live their lives to the fullest.
Child care will be provided by a group of different healthcare specialists. They will assist in developing a care plan outlining the assistance and therapies that the kid may require.

1. Feeding and diet are beneficial.
It is critical for persons with SMA, especially youngsters, to get the proper nutrients. This promotes healthy growth and development.

  • A dietician can provide feeding and dietary guidance.
    • A feeding tube may be required if the youngster has trouble feeding or swallowing. A tube linked directly to the stomach via the skin of the tummy (gastrostomy tube) or a tube going through the nose and down the throat can be used (nasogastric tube).
  • Breathing exercises help improve the respiratory muscles and make coughing easier
    • A suction machine to help counter the throat if necessary - this involves inserting a thin, plastic tube into the back of the throat and sucking any mucus out.
    • In more severe circumstances, a machine delivers air through a mask or tube.
  • Walking frames and wheelchairs are examples of mobility equipment.
    • Arm or leg restraints (splints or braces)
    • Shoe inserts that enable walking more comfortable (orthotic)
Loss of muscle control, movement and strength
Gradually loses the ability to walk, sit or stand

Is there a cure/medications for spinal muscular atrophy type i?

Medications for spinal muscular atrophy I:

To treat SMA, the FDA has approved three medications: nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma), and risdiplam (Evrysdi). Both are types of gene therapy that work on the genes that cause SMA. The SMN1 and SMN2 genes direct your body to produce a protein that aids with muscle movement regulation.

1. Nusinersen (Spinraza): The SMN2 gene is altered by this medicine, allowing it to create more protein. It is appropriate for both children and adults with SMA. Medical personnel will inject the medication into the fluid that surrounds the child's spinal cord. This could take at least 2 hours to complete, including preparation and rest time, and will need to be repeated numerous times, with another dose every 4 months. According to studies, it benefits approximately 40% of those who use it by making them stronger and reducing the progression of the disease.

2. Abeparvovec-xioi onasemnogene (Zolgensma): This entails replacing the problematic SMN1 gene. It is intended for youngsters under the age of two. The medical team will insert a tiny tube called a catheter right into a vein in your child's arm or hand (an IV). Then they'll insert a replica of the SMN gene into a specific set of motor neuron cells via the tube. This will only need to be done once.
In studies, the onasemnogene abeparvovec-xioi aided children with SMA in meeting developmental milestones such as regulating their heads and sitting without assistance.

3. Risdiplam (Evrysdi): This medication works by preventing the SMN2 genes from interfering with protein creation, enabling the protein to enter the nerve cells when necessary. Your youngster should take it once a day, after a meal. Their weight determines the dosage. Clinical research revealed that 41% of people taking it had a better muscular function after 12 months.

Loss of muscle control, movement and strength
Gradually loses the ability to walk, sit or stand

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