Spinal muscular atrophy (SMA) is an autosomal recessive, inherited neuromuscular disease. It is characterized by progressive loss of motor neurons within the spinal cord, leading to progressive muscle weakness and atrophy. Muscle movement is controlled by these motor neurons; whose disruption interferes with the signals between motor neurons and muscles; leading to progressive weakness and wasting.
SMA is the second most common inherited disorder with a global incidence of about 1 in 6,000 live births. Its carrier frequency is 1:40 for the Type I and 1:80 for the juvenile form (type III)3. The SMA incidence in the Middle East is 40 times higher than the Western world. It ranges from 10 to 193 per 100,000 births, primarily due to the increased rate of consanguineous marriages.2 The latter might have contributed to the high SMN1 carrier frequency in the Middle East, estimated at 1:20, compared to the global rate reaching up to 1:100.
Deletion of the survival motor neuron (SMN1) 1 gene on the long arm of chromosome 5 is the most common form of SMA. SMN1 gene produces a protein called SMN1, whose function is to maintain the integrity of motor neurons. The absence of this protein causes progressive degeneration of anterior horn cells. Another homologous gene, SMN2, is located in chromosome 5. Due to a phenomenon known as an alternative mRNA splicing, SMN2 is able to produce a small amount of full-length, functioning SMN1 protein. Therefore, the number of SMN2 copies in a given patient modulates the severity of the disease with a higher number predicting a milder disease.3,
SMA patients present in four forms depending on the motor acquisition and the age of presentation. Infantile-onset SMA type I, also known as the Werdnig-Hoffmann disease, is the most common type accounting for 60% of all cases. Typically, symptoms start before 6 months of age with reduced in utero movements leading to arthrogryposis, severe hypotonia, and breathing difficulties; culminating in death in the first two years of life, if left untreated.1
SMA type II, or the intermediate form, starts to manifest between 6 and 18 months of age. Affected children can sit but not stand or walk. They might also experience respiratory difficulties including hypoventilation in sleep. If not treated, the development of disease is unpredictable, but most affected individuals live into adolescence or young adulthood.1
In SMA type III, affected children develop symptoms after 18 months of age and can walk independently5. Symptoms start by showing difficulties with daily activities such as walking, running, climbing steps, and rising from a chair. The proximal leg muscles are initially affected followed by the proximal upper extremities.
In SMA type IV, individuals develop symptoms after 21 years of age, with mild proximal muscle weakness, which typically does not interfere with ambulation and independent living. In addition to the neuromuscular manifestations, recurrent respiratory infections, scoliosis, and joint contractures are common complications of SMA. A comprehensive, multidisciplinary approach to SMA management prolongs patients’ lifespan and improves outcomes.4
The economic burden of the SMA, both directly and indirectly, is enormous; led by type I SMA with an estimated yearly inpatient cost exceeding $100,000. Furthermore, outpatient costs are 50 times higher than age-matched controls. Moreover, a study of hospitalization cost representing hospitals in 44 United States (US) states showed that the average inpatient cost for children with SMA type I was $150,921, whereas the admission cost for children with no chronic condition was $19,261.12 In addition, recent analysis shows that 73.5% of SMA patients need home health services and 60.6% require neurology and/or pulmonology outpatient care.7 Beside the high cost of health care for SMA patients, a tremendous cost for caregivers exists; who spend around 53 hours per week caring for patients. This leads to absenteeism and subsequent financial hardship in families.
To our knowledge, few studies describing the prevalence and carrier status of SMA in the Gulf region are present. Therefore, understanding the disease inheritance and demographics in the Kingdom of Saudi Arabia (KSA) is essential. In this study, an observational analysis of phenotypes and genotype of an SMA cohort seen in a tertiary care hospital in KSA was done. To our knowledge, this is the first study that describes this population in KSA.