In general, the earlier the symptoms appear, the shorter the life span. The onset is sudden and dramatic. Once symptoms appear the motor neuron cells quickly deteriorate shortly after. The disease can be fatal and there is no cure for SMA yet known. The major management issue in Type 1 SMA is the prevention and early treatment of respiratory infections; pneumonia is the cause of death in the majority of the cases. The average life expectancy is 1 year for Type 1 SMA. 20 years for Type 2 (sometimes longer), and Type 3 can life a normal life span. People with SMA are very Intellectual. Their sexual functions are unaffected by SMA.
A severe infantile form of the disease can also occur in boys because of missense and synonymous variants mutations in gene UBE1 on the X chromosome. Sons of women with this genetic mutation generally have a 50% chance of suffering the disease, and daughters of women with the mutation have a 50% chance of being carriers, while unaffected by the disease itself.
All forms of SMN-associated SMA have a combined incidence of about 1 in 6,000. SMA is the most common cause of genetically determined neonatal death. The gene frequency is thus around 1:80, and approximately one in 40 persons are carriers. There are no known health consequences of being a carrier, and the only way one may know to consider the possibility is if a relative is affected.
The most common form of SMA is caused by mutation of the SMN gene, and manifests over a wide range of severity affecting infants through adults. This spectrum has been divided into three groups, depending on the age of onset, and are as followed:
|Group||Name||General age of onset||Description|
|Infantile SMA||Type I or Werdnig-Hoffmann disease||0-6 months||SMA type I, also known as severe infantile SMA or Werdnig Hoffmann disease, is the most severe, and manifests in the first year of life. This type generally onsets quickly and unexpectedly after birth; babies diagnosed with Type I SMA do not generally live past one year of age. Pneumonia is considered the ultimate cause of death due to deterioration of survival motor neurons; motor neuron death causes insufficient functioning of the major bodily organ systems, particularly respiratory (e.g. breathing, ridding of pooled secretions inside lungs).|
|Intermediate SMA||Type II||7-18 months||Type II SMA, or intermediate SMA, describes those children who are never able to stand and walk, but who are able to maintain a sitting position at least some time in their life. The onset of weakness is usually recognized some time between 6 and 18 months. Weakness slowly and gradually increases over the life of the individual.|
|Adult SMA||Type III or Kugelberg-Welander disease||>18 months||SMA type 3 describes those who are able to walk at some time.|
Infantile X-Linked SMA is similar to but distinguishable from Werdnig Hoffmann disease, manifested at or before birth in boys. Boys and Girls who inherit the gene usually die before age 2. If both parents have the gene the likely hood of another child not carrying the gene is 25% if they themselves do not develop it.
Although gene replacement strategies are being tested in animals, current treatment for SMA consists of prevention and management of the secondary effect of chronic motor unit loss. It is likely that gene replacement for SMA will require many more years of investigation before it can be applied to humans. Due to molecular biology, there is a better understanding of SMA. The disease is caused by deficiency of SMN (survival motor neuron) protein, and therefore approaches to developing treatment include searching for drugs that increase SMN levels, enhance residual SMN function, or compensate for its loss.
Much can be done for SMA patients in terms of medical and in particular respiratory, nutritional and rehabilitation care. However, there is currently no drug known to alter the course of SMA. Significant progress has been made in preclincial research towards an effective treatment. Several drugs have been identified in laboratory experiments that hold promise for patients. To evaluate if these drugs benefit SMA patients, clinical trials are needed. In a clinical trial a new medication is tested while the patients are carefully monitored for their safety and for any possible drug effects, positive or negative.
Some drugs under clinical investigation for the treatment of SMA:
In 1978 Pearn published a series of papers on SMA. He reported that childhood onset SMA is not an uncommon disease and has an incidence in the Northern UK in range of 4 per 100,000 births. At that time the association between the severe infantile form of SMA and the milder forms was not understood. With the advantage of knowledge about the causative gene, it is now known that SMA1, SMA2 and SMA3 are all caused by mutations in the same gene. The overall incidence of SMA, of all types, is in the range of 1 per 6,000 individual. It affects individuals of all races, unlike other well known autosomal recessive disorders like sickle cell disease, and cystic fibrosis, that have significant differences in occurrence rate between races. Overall, SMA1 is the most common genetic cause of death in infants.
The autosomal recessive versions of SMA are caused by inheritance of a mutated gene from each parent, who would not know that they have the abnormal gene because having only one mutated copy produces no symptoms. Once a child is affected, each subsequent baby has a 25% chance of having the illness. If a sibling does not inherit the disorder, he or she has a 2/3 chance of being a carrier.
On the other hand, X-linked infantile SMA is passed from mothers only to sons. Sons have a 50% chance of inheriting the defective gene from a mother who is a carrier and suffering the disease, while daughters have a 50% chance of becoming carriers without symptoms themselves. Couples may want to have genetic counseling before deciding to have more children. Counseling is available to these families through the community.
In 1990 mapping of the gene for SMA to chromosome 5q11.2-13.3 was reported and culminated in a 3 year research funded in part by the Muscular Dystrophy Association. The findings were also confirmed by French researchers. The identification of the gene for autosomal recessive SMA on chromosome 5q has allowed for prenatal diagnosis. Families who are at risk, or who have had a child with the diagnosis can have an amniocentesis done during pregnancy for DNA testing.
Although SMA often results in death during childhood, some people with SMA survive into adulthood and even old age. Actual lifespan depends greatly on the severity of SMA in each individual, and the three major types of SMA provide only a rough diagnostic guide; however even some individuals diagnosed with type-1 SMA survive to adulthood. Intellectual ability is unaffected by SMA, and adults with SMA benefit greatly from the use of assistive technology, such as speech recognition or Switch Access software. Such devices allow people with even very limited mobility to use a computer to read, write, communicate, play video games, and access environmental controls. Sexual response and reproductive functions are also unaffected by SMA; individuals with SMA can enjoy active sex lives and have given birth to children.
One example of an adult living with SMA-I is Ami Ankilewitz, who was 34 years old as of 2005, outliving his predicted life expectancy by 28 years. His experiences are presented in the documentary 39 Pounds of Love, whose title refers to his total body weight.
AmandaDi is 26 years old (born 1982) and lives in Texas. In 2007 she graduated from Tarleton State University with a double major in Business Management and Business Administration. She is now pursuing a Masters degree in Human Resource Management. Amanda's website is Independence4Amanda
Keith Hogan of Austin Texas recently turned 43 years old. He was originally diagnosed with SMA Type 1; however, as he continued to outlive his doctors' predictions, the diagnosis was changed to 'presumed' SMA Type 2. You can learn more about Keith in a short documentary called The Lucky Mutant.
Matt Boggan, who turned 40 in March, 2008, was also originally diagnosed with SMA Type 1. He is a practicing attorney in Knoxville, Tennessee.
Nicole Roberts, is 37 years old (born in March 1971) with SMA Type I-II. She is a well known and respected psychic, animal communicator, and spiritual counselor living in Minneapolis, Minnesota.
David M Hooker is 72 years old (Born in August 1936) with SMA Type I-II. He has three biological children with no symptoms. He lives in Wichita, KS. He was diagnosed in 1969 at the age of 33 and has well outlived all expectations. He has been to the Mayo Clinic in Arizona and undergone tests to determine how he has survived for so long. He is the oldest known person with SMA. He still lives on his own and walks on his own with the assistance of braces.
On March 15th 2006, the High Court of Justice of England and Wales ruled that 17 month old "Baby MB" (identity withheld) was to be kept alive, contrary to 14 medical professionals' advice - one of the medics 'Dr. S' stating "I think that the cumulative effect of the condition's effects is that he has an intolerable life" . The judge said that "he felt the child gained enough pleasure from life to outweigh the medical evidence of his condition" .
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