SPINAL MUSCULAR ATROPHY (SMA)
Article by : Dr Rick Leventer MBBS BMedSci FRACP Peadiatric Neurologist Dept. of Neurology Murdoch Childrens Research Institute Royal Childrens Hospital Melbourne
What is it?
SMAs are a group of related diseases resulting in worsening muscle weakness due to progressive loss of motor nerve cells (neurons) in the spinal cord (and brainstem).
The motor neurons in the spinal cord are also known as anterior horn cells, and relay the messages for muscle movement from the nerve cells in our brains, to the muscles in our limbs, chest, throat, face and mouth.
SMAs are not diseases of the brain, the muscles or the sensory nerves (the nerves that relay feelings back to our brains). The muscles do however eventually weaken and get smaller (atrophy) because they do not receive stimulation from motor neurons.
How many types are there?
SMAs are the most severe forms of Motor Neuron Disease, and usually begin in childhood. Four main forms have been described depending on their severity and age of presentation. These are (from most severe to least severe) as follows:
- SMA type I (also known as infantile SMA or Werdnig-Hoffman disease)
- SMA type II (also known as intermediate SMA or chronic childhood SMA)
- SMA type III (also known as juvenile SMA or Kugelberg-Welander disease)
- SMA type IV (also known as adult onset SMA)
What are the clinical features?
The main clinical feature is muscle weakness. The weakness is progressive, and involves muscle of the limbs, trunk, chest, face, throat and mouth.
In SMA type I, children may be born weak, or develop weakness within the first weeks or months of life. The weakness initially affects movement, but later also affects the ability to take deep breaths, cough and swallow.
The inability to cough or swallow effectively places children at risk of repeated chest infections, which get harder and harder to recover from. The inability to swallow effectively necessitates feeding using a tube placed into the stomach. SMA does not affect the brain, so intelligence and comprehension are normal. SMA does not affect the sensory nerves, so children have normal feeling of touch, temperature and pain.
What is the cause?
SMA types I and II are due to abnormalities of the SMNI gene (the Survival Motor Neuron I gene). If the SMNI gene has reduced or no function, then the motor neurons in the spinal cord and brainstem do not survive, and gradually die off.
The SMNI gene is located on chromosome 5. We all have two copies of this gene. In SMA types I and II, the children have two faulty copies of the SMNI gene. In most cases, they have inherited the faulty gene from their parents. Their parents are not affected as they have a normal backup copy of the SMNI gene, and thus are carriers.
SMA is inherited in an autosomal recessive pattern, meaning that if two carriers have children; there is a 25% chance (one in four) of having an affected child in each pregnancy.
How is it diagnosed?
SMA is suspected clinically by the history of early onset weakness and the examination findings of weakness and loss of reflexes (such as the ankle jerk).
Some children also have fine twitches of the muscles in their limbs or tongue known as fasciculations. Fasciculations are a sign of sick or dying motor neurons.
Occasionally electrical tests known as nerve conduction studies are carried out which can show that the weakness is likely due to a problem in the anterior horn cell.
In the last five years a specific genetic test can be performed on DNA to look for abnormalities of the SMNI gene, and thus confirm the diagnosis.
Is there a treatment?
Unfortunately, there is no cure for SMA.
Doctors and scientists have not yet been able to stop or reverse the death of motor neurons, or repair the faulty SMNI genes.
Treatment therefore revolves around treating the child's symptoms (such as chest infections and inability to feed), and keeping them happy, comfortable and stimulated.
Research and Future Directions!
Research groups all over the world are trying to develop better treatments or even a cure for SMA.
Most of the research is aimed at either keeping the SMNI gene from dying, or stimulating similar genes (such as SMNII) to take over the function of the faulty SMNI genes.
This involves using certain medications or genetic manipulations.