Spinal muscular atrophy (SMA) is a hereditary disease that is also the most common autosomal recessive disease that causes death in the first years of life. It is characterized by the degeneration of the lower alpha-motoneuron (in the anterior horn of the spinal cord). Its incidence is about 1:6000 to 1:11000 live births. Respiratory complications of the disease are the main cause of mortality and morbidity. Ineffective cough, hypoventilation during sleep and recurrent infections are consequences of impaired respiratory function. The ultimate goal should be to reduce the frequency of infections and the duration of hospitalizations. Muscle weakness caused by impaired neural function also leads to feeding difficulties and gastroenterological manifestations of the disease. Difficulty swallowing, gastrointestinal dysfunction and gastroesophageal reflux are common problems as well as an increased risk of food aspiration and aspiration pneumonia. Impaired motor function inevitably leads to the development of contractures, spinal deformities and an increased risk of fractures due to osteopenia. Signs appear in infancy or childhood. There are different types that can include hypotonia, hyporeflexia, difficulty sucking, swallowing and breathing, developmental delays and, in severe cases, early death.
Spinal muscular atrophies are caused by autosomal recessive mutations of one gene locus on the short arm of chromosome 5, which causes a homozygous deletion. There are 4 forms (types) of the disease.
Type I spinal muscular atrophy (Werdnig–Hoffmann disease) is present in utero or becomes symptomatic at approximately 6 months of age. Patients have hypotonia (at birth), hyporeflexia, tongue fasciculations, and difficulty sucking, swallowing, and breathing. Due to respiratory failure, 95% children die by the age of 1 year, and all die by the age of 4 years.
IN type II (intermediate) spinal muscular atrophy, Symptoms usually appear between the ages of 3 and 15 months; <25% affected children learn to sit, and none of them learn to walk or crawl. Children have flaccid muscle weakness and fasciculations that are difficult to notice in young children. Deep tendon reflexes are absent. Dysphagia may be severe. The disease is often fatal in early life, usually due to respiratory complications. However, progression of the disease may stop spontaneously, but permanent non-progressive weakness remains, with a high risk of developing scoliosis and its complications.
Type III spinal muscular atrophy (Wohlfart–Kugelberg–Welander disease) begins between the ages of 15 months and 19 years. Pathological findings are similar to type I, but the disease progresses more slowly, so sufferers live longer; some patients have a normal lifespan. Some familial cases are the result of damage to specific enzymes (e.g., hexosaminidase deficiency). Symmetrical weakness and muscle wasting are most noticeable in the legs (the process progresses from proximal to distal), and first affects the quadriceps and hip flexors. Later, it also affects the arms. Life expectancy depends on the development of respiratory complications.
Type IV spinal muscular atrophy It can be recessive, dominant, or X-linked. The disease begins in adulthood (30 to 60 years) and progresses slowly, primarily characterized by proximal muscle weakness and muscle wasting. It is sometimes difficult to distinguish this disorder from ALS, because ALS predominantly affects lower motor neurons.
