RÉSUMÉ
BACKGROUND: Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations. METHODS: We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates. RESULTS: Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment. CONCLUSIONS: The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.
The occurrence of spinal muscular atrophy, a fatal genetic nerve and muscle disease, has been poorly studied in most Arab countries. Individuals who carry a single mutated gene copy (carriers) may be more likely to marry other carriers in regions where marriage rates amongst relatives, who share similar genetics, are high. Here we report the results of a newborn testing program for this disease in 1502 Emiratis and calculate the presence of carriers (1/79) and occurrence of disease (1/7122) in this population. Using this new information along with the annual birth and marriage rates in the United Arab Emirates and Saudi Arabia, we make the case that premarital genomic screening (carrier testing) is the best way to prevent this and other similarly inherited disorders in the Arab population.
