SMA literature dari Stanford

Wah, lama sekali nggak diupdate nih.
Berikut di copy dari Stanford:
About Spinal Muscular Atrophy
OverviewSpinal muscular atrophy (SMA), a genetic disease that affects approximately 1 in 10,000 live births, is the second most common childhood neuromuscular disease after Duchenne muscular dystrophy. It affects motor neurons in the spine. One of the key symptoms is progressive weakness, usually characterized by the need for assistance in sitting or standing and often progressing to the point the patient needs to use a wheelchair. The more severe manifestations can result in babies appearing "floppy" and failing to reach key motor milestones, like lifting their heads independently. These babies may also lose progress that they have already gained in movement and function

Genetic Background: How do you get SMA?The main cause of SMA is a mutation (change) in a person's chromosomes. Our DNA holds all of our genetic information and it is contained in 23 pairs of chromosomes (except in very rare cases). Every pair of chromosomes consists of one from each parent. Two parents that don't have SMA might both still have an "SMA" mutation in one Chromosome 5 (yes, they have very creative names). As long as that same piece of the other Chromosome 5 is unaffected neither parent will show any symptoms. That makes the disease recessive. It is possible, however, that these same parents can give their child two of these "SMA" versions of Chromosome 5. If that happens, the child doesn't have an unaffected one for backup, and will likely have SMA. The parents can still pass on this "SMA" version of the chromosome even though they don't have SMA, so they are called carriers.
Because Chromosome 5 is an autosomal chromosome (compared with the X and Y chromosomes that determine gender), both boys and girls have an equal chance of getting SMA. Additionally, the affected chromosomes don't "run out" after the parents have a certian number of children with SMA. Each time the parents have a child there is still a 50:50 chance of each parent passing on an "SMA" chromosome. The chance of that child getting both "SMA" ones is then 1 out of 4, or 25%. Half of the time, the child could have one unaffected and one "SMA" chromosome and be carriers, just like the parents. Another 25% of the time, the child could have both unaffected chromosomes. For more discussion of autosomal recessive inheritance and its application to SMA, please see the links below under the "Genetics" subheading. In the meantime we will return to the specifics of SMA.

More on the Genetics of SMA:There is a vital protein for our motor neurons (cells that send the signals from our brain and spinal cord to our muscles), called Survival of Motor Neuron, abbreviated SMN. The primary gene (small piece of the chromosome) on Chromosome 5 that holds the information needed to make this protein is called SMN1. It is the one that can be mutated to cause SMA.
The discussion gets more complicated when we bring in the fact that there are actually two types of genes that can make SMN protein and they both play a role in how serious a person's symptoms will be. In addition to SMN1, another gene called SMN2 looks a lot like SMN1 and can make some SMN protein. Most of the SMN mRNA* made from the SMN2 gene is missing an important piece, however: "Exon 7." As a result, the SMN protein produced is shorter and doesn't work properly. Many of the medications currently under investigation as possible treatments for SMA involve trying to get SMN2 to make more proteins in general, or otherwise trying to get the SMN protein made from SMN2 to look like the bigger SMN normally made from SMN1 more of the time. It has also been shown that in many cases (but not always) the more copies of SMN2 that someone with SMA has, the less severe his or her symptoms are likely to be. Without any SMN1 or SMN2 genes, a baby will not survive through a full term of pregnancy.
*(In order to make a protein, we first make a piece of mRNA - the "m" stands for "messenger" - that takes the gentic information from the chromosome to the place in our cells where proteins are made. )

Clinical Concerns:Due to muscle weakness, the key areas of concern for anyone with SMA are Pulmonary (breathing), Gastrointestinal (nutrition and digestion), and Orthopaedic (posture, joints, and mobility), and usually in that order. A doctor should be consulted in each of these specialties with appropriate consideration given to the issues discussed in the Standard of Care Consensus. Ideally, we all want to maximize fuctionality and minimize risks and discomfort in all of these areas for SMA patients, and a committe of experts nationwide in SMA has compiled the relevant information for the consensus statement. What follows in this section merely provides a very brief overview. A more thorough outline is also available at the SMA at Stanford: Standard of Care page.

Pulmonary/Respiratory issues in particular pose a threat to patients with SMA, especially those with Type I and severe Type II. At the most basic level, weakness in breathing muscles mean that a patient may not get enough oxygen to the blood, espeically while he or she is sleeping. These same patients are also at risk for aspiration, breathing food or even their own secretions/saliva into their lungs, because they may not close their airways completely during swallowing. Respiratory illness, especially pneumonia, is often a big problem for SMA patients due reduced cough effectiveness. Fortunately, there is a great deal of noninvasive ventilation equipment that has been found to help minimize the effects of these problems for many SMA patients: "cough assist," suction, and IPV to help manage secretions, and BiPAP to help with breathing.
Gastrointenstinal issues arise from weakness in digestive muscles and the closures between sections of the GI tract (sphincters). Patients can suffer from reflux or constipation, for example. Also, if a Type I or II patient has significant enough trouble with the chewing and swallowing muscles, families may opt to include dietary supplements or have a feeding tube put in to ensure adequate nutrition.
Overall, the greatest Orthopaedic interventions seem to center around maximizing mobility and in some cases pain management, too. Depending on severity SMA's complications can include: joint contractures, scoliosis, impaired balance, and limited range of motion. SMA does not affect patients' intelligence or phychological capacities, and physical and occupational therapy in combination with wheelchairs, orthotics, surgery, etc. can often help people with all Types of SMA go to school, work, and participate in a wide variety of activities.
http://sma.stanford.edu/smainfo.html