Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that affects the motor neurons of the spinal cord and leads to increasing muscle weakness. The disease is progressive in nature, weakness begins with the whole body and the muscles of the legs, and then it reaches the muscles responsible for swallowing and breathing. At the same time, the intelligence of patients with SMA is absolutely preserved. SMA is a common genetic disease from the rare category. The main goal of this research work is a detailed analysis of SMA disease with the identification of its etiology, types, symptoms, and signs.
Etiology
Mutation in the SMN1 gene is a cause of SMA, which normally produces the SMN protein. According to Ahmad (2016), “SMN is a ubiquitously expressed protein, but why selectively lower spinal cord motor neurons degenerate remains unclear” (p. 2).
Due to gene mutations, people with SMA produce less SMN protein, resulting in loss of motor neurons. Progressive degeneration and loss of motor neurons in the brain stem and anterior horns of the spinal cord lead to atrophy and muscle weakness. According to Carson et al. (2018), in most cases of this disease, in exon 7 of the SMN1 gene, chromosome 5q13 has a homozygous deletion, but one and several more copies of the motor neuron 2 survival gene (SMN2) are preserved. The production of a truncated, non-functional SMN protein occurs due to the mutant SMN1 gene, while the SMN2 gene can produce only a small amount of functional SMN (somewhere around 10%), which causes SMN.
Types
Depending on the severity of the symptoms, 4 main types of proximal SMA are distinguished: SMA I, SMA II, SMA III, SMA IV. According to Farrar et al. (2017), type I – Infant usually occurs in the first 6 months of a baby’s life. Children lack motor development, have difficulty breathing, have difficulty sucking and swallowing, do not hold their heads, or sit on their own. Type II – Intermediate, observed in children aged 7 to 18 months.
Children with this form of spinal amyotrophy can eat, sit, but they will never walk without assistance. Type III – Youthful, occurs in children older than 18 months. The patient is able to stand, but experiences severe weakness, with a tendency to disability (movement in a wheelchair). Type IV – Adult, appears in adults over 35 years old. Does not affect life expectancy significantly; it can lead to a weakness of the proximal muscles, fasciculations, decreased tendon reflexes.
Physiopathology
How the disease will develop, how many years the child will live, depends on the type of the disease. With atrophy of Type I, the prognosis is extremely unfavorable. About 50% of babies do not live up to two years. According to Farrar et al. (2017), more than 10% of children with Werding-Hoffman’s disease can live up to 5 years. The cause of death is most often pneumonia, respiratory arrest, heart failure.
Patients diagnosed with Dubovitz disease live on average up to 10, 12 years. About 30% of babies die before they are four years old. In type III SMA, infant mortality is less common. In many patients, symptoms appear in pre-adolescence. After a few years, they stop walking. Further, on the rise, atrophy of the muscles of the internal organs, including the respiratory, is noted. Type IV disease is not considered to affect the life expectancy of patients; however, it leads to disability.
Clinical Manifestations of SMA
Type 1 SMA (Werding-Hoffman atrophy) is available for detection during pregnancy. The doctor can suspect disease in the fetus with very sluggish movements. But it is not very easy to confirm the diagnosis at the stage of bearing a child, and this usually occurs after childbirth. A kid with such atrophy cannot hold his head himself, toss and turn from side to side, does not sit down. He lies almost constantly on his back, his posture is relaxed, he does not raise his legs, he does not bring them together, he does not put his palms together. At the earliest stage, there can be considerable problems in feeding the baby, because swallowing it turns out very badly or fails. Some manage to live up to seven to eight years, but atrophy only intensifies. Usually, death occurs due to insufficient functioning of the heart, lungs, and digestive organs.
Type 2 SMA (Dubovitz atrophy) is usually not found at birth, because the baby is able to breathe, swallow food, and only after six months does the progress of muscle atrophy become apparent. According to Farrar et al. (2017), “Patients with SMA type II have a better prognosis than those with type I disease, with 93% surviving to 25 years” (p. 355). If the first symptoms occur at the age when the child has already learned to stand in the crib, then a striking sign may be the mowing of the legs, the causeless falls of the crumbs. Gradually, it becomes difficult for him to swallow. Over time, the child begins to need a wheelchair.
Type 3 SMA (Kugelberg-Velander amyotrophy) can be detected at any age after 2 years to adulthood. A child who normally grows and develops gradually begins to complain of weakness, usually in the shoulders and forearms. As he progresses, it becomes difficult for him to run, walk up the stairs, and crouch. It all depends on the care – some retain the ability to move independently for many years. Type 4 SMA (Kennedy atrophy) is found only in male patients since it is considered linked to the sex chromosome X. The first signs are weakness in the femoral muscles, and the cranial nerves are gradually affected, at the same time the disease progresses slowly.
Medical Management
Unfortunately, today medical science cannot offer methods and means for treating SMA. A systematic intake of drugs that enhance energy metabolism at the cellular level, B vitamins, nootropic drugs, as well as potassium and nicotinic acid preparations, is also recommended. It is shown that a child with SMA adheres to a high protein diet, but recent studies have shown that the role of the diet is somewhat exaggerated – there is no evidence that high protein in food at least somehow affects the rate of progression of the disease.
According to Glascock et al. (2018), “Other approaches to therapy at the level of increasing SMN protein levels, including a gene transfer approach using an AAV9 vector or small molecule modification of SMN2 splicing, are in promising clinical trials” (p. 146). Medical massage, UHF, electrophoresis, respiratory gymnastics programs to maintain respiratory muscles, and swimming will help extend the period of a more or less full life.
Conclusion
Spinal muscle atrophy today remains common rare diseases transmitted genetically. The probability of transmission of CMA by the carrier is rather high, especially if the carriers are two parents. Prevention of this disease now does not exist, since, in particular, it is inherited, and it is only possible to predict it in the fetus. Unfortunately, it is also not possible to recover from any type of SMA, following the course of treatment can only extend the patient’s life. It could be that future researches and medical discoveries may help cure the disease or at least alleviate the symptoms because it has great potential.
References
Ahmad, S., Bhatia, K., Kannan, A., & Gangwani, L. (2016). Molecular mechanisms of neurodegeneration in spinal muscular atrophy. Journal of experimental neuroscience, 10(2), 1-5.
Carson, V. J., Puffenberger, E. G., Bowser, L. E., Brigatti, K. W., Young, M., Korulczyk, D.,… & Strauss, K. A. (2018). Spinal muscular atrophy within Amish and Mennonite populations: Ancestral haplotypes and natural history. PloS one, 13(9), 1-18.
Farrar, M. A., Park, S. B., Vucic, S., Carey, K. A., Turner, B. J., Gillingwater, T. H.,… & Kiernan, M. C. (2017). Emerging therapies and challenges in spinal muscular atrophy. Annals of neurology, 81(3), 355-368.
Glascock, J., Sampson, J., Haidet-Phillips, A., Connolly, A., Darras, B., Day, J.,… & Prior, T. (2018). Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening. Journal of neuromuscular diseases, 5(2), 145-158.