Both of these diseases are diseases inherited from parents to their children and have different characteristics. Between the two diseases, Spinal Muscular Atrophy is more frequent cause of death in infants.
This paper attempts to give an explanation of the incidence of disease, patterns of inheritance, and research efforts to find a cure.
Spinal Muscular Atrophy (SMA)
SMA is a genetic disease muscle-nerve (neumuscular genetic disorder) is characterized by muscle paralysis. Although the clinical appearance of the real from SMA patients is muscle paralysis, especially in the second leg.
The main source of paralysis was not caused by damage to the muscle cells themselves. Paralysis that occurs purely due to the destruction of nerve cells in the spinal cord (spinal cord). This is different from muscular dystrophy in which the damage did occur in the muscle itself.
The meaning of the spinal cord (spinal cord) in this paper is part of the central nervous system that runs continuously from the brain down to the lower back. From this exit the spinal cord neural branches are responsible for different parts of the body, including limbs and toes.
Muscular movements, as we know, is controlled by the brain through the medium of the spinal cord, where the nerves that connect the brain to the muscles through the spinal cord.
Thus it is understood that damage nerve cells in the spinal cord causes loss of motor control, especially in the muscles responsible for movements such as crawling, walking, chewing, head and neck control and even breathing.
In this case the leg muscles and breathing is more frequent and more severe paralysis compared to other muscles. Cause muscle paralysis is never used, so that makes it shrink (atrophy), especially noticeable in the feet.
The types of SMA
Based on its severity, SMA is divided into three types.
SMA Type I, also called Werdnig-Hoffmann Disease, is the most severe type.
Symptoms of SMA Type I started very early, from before birth or be the slowest since the age of 6 months after birth.
The symptoms were characterized by difficulty breathing, can not breastfeed and overall muscle weakness.
The main problem in babies SMA type I is a weakness in respiratory muscles, which makes it often relies on respiratory aids. Babies with SMA Type I have a very low life expectancy, in which all or nearly all die before the age of 2 years due to respiratory failure.
SMA Type II have less severity, when compared with type I.
The symptoms of SMA in type II begins between ages 6 to 18 months.
Children with SMA type II may sit unaided and can sometimes stand with difficulty holding on to his feet. However, none of which can be run.
Although life expectancy is higher than the SMA type I, in general, children with SMA type II had severe respiratory problems are the cause of death at the age of early childhood.
SMA type III or Kugelberg-Welander also called Disease, is the type with the lowest severity level.
The symptoms begin until after 18 months of age.
Usually begins with a normal motor development and later at the age of early childhood experienced a significant decline in motor skills. In rare cases, new symptoms began to emerge in adulthood (some experts call SMA Type IV).
Characteristics of molecular genetics in high school
The disease is caused by damage to the SMN1 gene is located on the long arm of chromosome 5 (5q also called). The majority (95%) patients in high school, had no SMN1, which is said to have SMN1 deletion.
While at about 3% of patients, SMN1 was there but suffered damage to the DNA sequence. A small percentage (2%) SMA patients did not show any abnormality in SMN1, called non-5q SMA.
SMA is derived from parent to child is autosomal recessive. In this case, both parents are carriers (carrier) damage to the SMN1 gene, but did not show symptoms or healthy high school.
For a genetic disease, high school is quite often the case with incidence of 1 in 6000-10000 live births. While 1 in 40 people are healthy carriers of damage to the SMN1 gene that does not show the symptoms of SMA.
If two carriers marry SMN1 gene damage, then there is probably 25% of children who are born will suffer from high school. While there is a possibility of 50% of children will be born healthy but be carriers of the SMN1 gene damage and 25% percent chance of children who are born healthy and have the SMN1 gene is also healthy.
What's interesting is that the SMA gene SMN1 gene actually has a twin that is located right beside him on the long arm of chromosome 5, called SMN2 gene. These two genes, SMN1 and SMN2 has a DNA sequence is 99.9% the same and should be able to produce the same protein, called SMN protein.
Another interesting thing is, although 95% of SMA patients experience a loss (deletion) SMN1, none of the patients also experience a loss of SMN2.
The question then, if the SMN1 and SMN2 has a DNA sequence is 99.9% the same, why the presence of SMN2 can not replace the loss of SMN1? This question has become the 'million dollar question' in studies of high school, the answer is because exploration has led investigators in these studies to cure SMA.
DNA sequence differences between SMN1 and SMN2 is only 0.01% that was very, very important for function or absence of each gene. In SMN1, its DNA sequence allows it to function normally and produce the functional SMN protein. While in SMN2, its DNA sequence made him unable to function normally where SMN protein produced is not functional.
From this description unanswered why the presence of SMN2 in all SMA patients can not replace the damage or loss of SMN1. Nevertheless, the presence of SMN2 in all SMA patients raises hopes to find a cure for SMA research.
If SMN2 can be manipulated in such a way so as to produce the functional SMN protein in sufficient quantities, then the possibility of cure or at least reduce the severity of SMA patients can be expected.
This is caused by two things:
1. Although SMN1 is lost or damaged in nearly all SMA patients, but its still intact SMN2.
2. DNA sequence similarity is very high between SMN1 and SMN2 makes SMN2 has the potential to provide the same function as SMN1.
This manipulation can be done with drugs or compounds of natural or synthetic as well as with molecular intervention by small molecules that are directed at manipulating the expression of DNA.
We have had a lot of research to examine these possibilities are conducted in various parts of the world, including Europe, America and also in Malaysia is no exception. Several studies in Europe and America have even entered the stage of clinical trials in patients who try it immediately.
However, not one of the drugs that are officially used in the clinic to treat patients with SMA. The researchers still need time to perform an optimization for efficacy and safety of these drugs.
Author
Dr. True to Haryo Sasongko
SMA researchers, working in the Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia
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