About werdnig hoffman disease
What is werdnig hoffman disease?
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 symptoms for werdnig hoffman disease?
Symptoms vary a lot, depending on the type of SMA:
Type 0. This is the rarest and most severe form of SMA and develops while you’re still pregnant. Babies with this type of SMA move less in the womb and are born with joint problems, weak muscle tone, and Weak muscles for breathing. They often do not survive due to breathing problems.
Type 1. This is also a severe type of SMA. A child may not be able to support their head or sit without help. They may have floppy arms and legs and problems swallowing.
The biggest concern is Weakness in the muscles that control breathing. Most children with type 1 SMA don't live past age 2 because of breathing problems.
Keep in touch with your medical team, family members, clergy, and others who can help give you the emotional support you need while your child fights this disease.
Type 2. This affects children 6-18 months old. The symptoms range from moderate to severe and usually involve the legs more than the arms. Your child may be able to sit and walk or stand with help.
What are the causes for werdnig hoffman disease?
SMA is a disease that's passed down through families. If your child has SMA, it's because they have two copies of a broken gene, one from each parent.
When this happens, their body won't be able to make a specific kind of protein. Without it, the cells that control muscles die.
If your child gets a faulty gene from just one of you, they won't get SMA but will be a carrier of the disease. When your child grows up, they could pass the broken gene to their own child.
What are the treatments for werdnig hoffman disease?
The FDA has approved three medications to treat SMA: nusinersen (Spinraza), onasemnogene abeparvovec-xioi (Zolgensma) and risdiplam (Evrysdi). Both are forms of gene therapy that affect the genes involved in SMA. The SMN1 and SMN2 genes give your body instructions for making a protein that helps with controlling muscle movement.
- Nusinersen (Spinraza). This treatment adjusts the SMN2 gene and lets it make more protein. It's used for both children and adults with SMA. Your child's medical team will inject the drug into the fluid around their spinal cord. Including preparation and recovery time, this can take at least 2 hours and will need to be done several times, followed by another dose every 4 months. Studies show it helps about 40% of people who use it by making them stronger and slowing the disease.
- Onasemnogene abeparvovec-xioi (Zolgensma). This involves replacing the problem SMN1 gene. It's used for children under 2 years old. Your child's medical team will put a tiny tube called a catheter directly into a vein in their arm or hand (an IV). Then, they'll send a copy of the SMN gene through the tube into a specific group of motor neuron cells. This will need to be done only one time. In studies, onasemnogene abeparvovec-xioi helped children with SMA reach certain developmental milestones faster, like controlling their heads or sitting without support.
- Risdiplam (Evrysdi). This treatment works to stop the SMN2 genes from disrupting the protein production, allowing the protein to reach the nerve cells as needed. Your child takes it orally once a day after a meal. The dosage is determined by their weight.Clinical trials showed improved muscle function after 12 months in 41% of those taking it.