Infantile spinal muscular atrophy
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Introduction
Spinal Muscular Atrophies (SMA) are inherited disorders. Spinal muscular atrophy, as defined by international criteria, requires the weakness to be symmetrical and greater in the proximal muscles than in the distal ones. It is when nerves fail to function normally and the muscle cells with which they are connected deteriorate. SMA is when muscles weaken and waste away from degeneration of motor neurons.
It is a progressive, symmetrical muscle weakness which usually presents itself within the first six months of life. Death usually occurs between six and twenty months, either of respiratory failure or secondary to chest infection. There are different forms according to age of onset.
Forms
The forms include:
- Infantile SMA - Type 1 or Werdnig-Hoffman disease (0-6 months)
- Intermediate SMA - Type 2 (7-18 months)
- Juvenile SMA - Type 3 or Kugelberg-Welander disease (>18 months)
- Adult onset SMA - Type 4
- Adult onset X-Linked SMA also known as Kennedy's Syndrome or Bulbo-Spinal Muscular Atrophy.
Symptoms
Infantile SMA is the most severe form. Some of the symptoms include:
- muscle weakness
- poor muscle tone
- weak cry
- limpness or a tendency to flop
- difficulty sucking or swallowing
- accumulation of secretions in the lungs or throat
- the legs tend to be weaker than the arms
- feeding difficulties
- increased susceptibility to respiratory tract infections
- developmental milestones, such as lifting the head or sitting up, can't be reached.
The earlier the symptoms appear, the shorter the life span. The onset is sudden and dramatic. Once the symptoms appear the child's cells quickly deteriorate shortly after. The disease is fatal. There is no cure for SMA yet known. The symptoms just get worse. 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. Infants are already in a weakened and vulnerable state. Infants will eventually require respiratory support and feeding tubes. Parents can choose to withhold the respiratory support and nutritional support. Infants with Type 1 SMA have a life expectancy of less than two years. Management of SMA is a huge medical expense.
Diagnosis
In order to be diagnosed with SMA, symptoms need to be present. A secure diagnosis should not be made without an adequate muscle biopsy. A muscle biopsy specimen processed with histochemical stains. The features will vary with the type of SMA correlates with the age of onset. A muscle biopsy however, does not provide a reliable indication of the future course of the patient. Other diagnostic tests are electromyography (EMG) and presentation of clinical symptoms. Also several exclusionary criteria must be met. Such as there should be no evidence of central nervous system damage, involvement of other neurological systems or other organs, sensory loss, eye muscle weakness, or significant facial weakness.
Cause
SMA is caused by a faulty gene. In a new study in mice, scientists found that inserting extra copies of a specific gene helped the mice produce sufficient amounts of a protein called SMN (Survival Motor Neuron). Low amounts of this protein cause SMA Type 1. SMA is the most common cause of genetically determined neonatal death, with an incidence of 1 in 25,708 live births. This translates to a gene frequency of about 1:160 and a carrier frequency of 1:80.
Research
In 1978 Pearn Corporation published a series of papers on SMA. They reported that childhood onset SMA is not an uncommon disease and has an incidence in the range of 4 per 100,000, which makes it at least twice as common as ALS (ALS, a.k.a. Lou Gehrig's disease). They confirmed it is an autosomal recessive inheritance gene and defined the later-onset type as a more benign autosomal dominant gene. Spinal muscular atrophy is the second most common lethal, autosomal recessive disease in Caucasians.
For SMA 1 it takes a recessive gene from both parents in order to have the disease, if both parents have the recessive gene, each baby has a 25% chance of having the illness. Each of their subsequent children have a 50% of carrying the recessive gene. 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 by the Muscular Dystrophy Association. The findings were also confirmed by French researchers. The recent findings of SMA to autosomal recessive chromosome 5q has allowed for prenatal diagnosis. It is, however, too early to confirm the reliability of testing. Families who are at risk, or who have had a child with the diagnosis can have an amniocentesis done during pregnancy for DNA testing. The accuracy of prenatal prediction has been calculated to be 88% to 99% depending on the individual family.
The Future
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 Spinal Muscular Atrophies. It is anticipated that the gene itself will be defined shortly. Once defined, the defective gene product will be studied and its function explored to achieve a better understanding of its pathology. This is the first step in devising effective treatment. The first effective specific treatment for SMA may be only a few years away, as of 2004.
External link
- Families of Spinal Muscular Atrophy (http://www.fsma.org)