Spinal muscular atrophy carrier frequency in Saudi Arabia

Abstract

Background: Spinal Muscular Dystrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Although no largescale popultion-based studies have been done in Saudi Arabia, it is reported that the incidence of SMA is higher in the Saudi population partly because of the high degree of consanguineous marriages. Methods:The final analysis included 4198 normal volunteers aged between 18 and 25 years old, 54.7% males, and 45.3% females. Whole blood was spotted directly from finger pricks onto IsoCode StixTM and genomic DNA was isolated using one triangle from the machine. To discern the SMN1 copy number independently from SMN2, Multiplex PCR with Dral restriction fragment analysis was completed. We used the carrier frequency and population-level data to estimate the prevalence of SMA in the population using the life-table method.Results: This data analysis showed the presence of one copy of the SMN1 gene in 108 samples and two copies in 4090 samples, which resulted from a carrier frequency of 2.6%. The carrier frequency was twofold in females reaching 3.7% compared to 1.6% in males. 27% of participants were children of first-cousin marriages. We estimated the birth incidence of SMA to be 32 per 100,000 birth and the total number of people living with SMA in the Kingdom of Saudi Arabia to be 2265 of which 188 are type I, 1213 are type II, and 8,64 are type III. Conclusion:The SMA carrier rate of 2.6% in Saudi control subjects is slightly higher than the reported global frequency of 1.25 to 2% with links to the high degree of consanguinity.

Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women

“…As of the current, SMA carriers screening is already open worldwide ( 14 , 27 – 29 ), and even has been conducted in most areas of China ( 16 , 17 , 19 , 30 – 34 ). In this study, we identified 726 SMA carriers from 39,647 participants who were screened for SMA in Lanzhou City, Gansu province.…”

Spinal muscular atrophy genetic epidemiology and the case for premarital genomic screening in Arab populations

“…A study from Morocco reported a carrier frequency of 1 in 25 and a prevalence of 1:1900, though this was based on a small sample of 150 Moroccan newborns 16 . While this work was in preparation, a study was published whereby screening 4,189 normal Saudi volunteers determined a carrier frequency of 1 in 38 17 . Using this SMA allele frequency, and the coe cient of inbreeding in Saudi Arabia 18 , we estimated SMA incidence in this country to be 1 in 3,192 (Table 1), which is consistent with that estimated by authors in this study (32 in 100,000 or 1 in 3,125 births) 17 .…”

“…Estimates of SMA births in UAE and KSA and the associated cost of postnatal treatment versus premarital screening Calculated by multiplying incidence in Table1by annual births in each country; # $2.1 million dollar; ^Calculated by multiplying cost of SMA testing ($50) per couple; $ calculated by multiplying the number of couples expected to have an SMA birth and requiring PGT/IVF (pre-implementation genetic testing/in vitro fertilization) by cost of PGT/IVF (30,000 USD 20 ); & calculated by subtracting cost of premarital screening and PGT/IVF from total cost of gene therapy We estimate the disease burden or incidence of SMA in the UAE. Using data from the UAE (this study) and Saudi Arabia17 , we demonstrate that, in addition to potentially preventing new SMA cases, premarital screening and subsequent PGT/IVF for at-risk couples, can be a highly cost-effective measure from a public health standpoint, leading to an expected 16 to 28-fold cost reduction compared to postnatal disease treatment. Interestingly, the cost savings due to premarital screening for this one disease (~$10 million in UAE and $324 million in KSA) is su cient to fund more comprehensive premarital genomic screening programs encompassing hundreds of recessive disorders in both countries.…”

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study

“…However, estimates suggest that it ranges from 1 to 2 per 100,000 individuals, with an incidence of 8–10 per 100,000 live births ( 15 ). Higher prevalence rates have been observed in Middle Eastern countries such as Saudi Arabia, where recent studies estimated roughly 2,265 SMA patients, possibly due to prevalent consanguineous marriages ( 16 ).…”

“…Canadian research involving over 900 patients and caregivers highlighted significant costs to families of SMA patients, with median health expenditures for assistive devices, healthcare professional services, and accommodation and travel, along with a notable negative impact on patient quality of life ( 20 ). Although SMA is a rare health condition, its incidence rate is believed to be increasing in the kingdom mainly due to high rate of consanguinity and allocating more financial resources for preventative (e.g., premarital screening) and early detection and treatment measures (e.g., newborn screening, early initiation of therapy) is necessary ( 16 ).…”