A landmark study by Sidra Medicine, a member of Qatar Foundation, has been featured in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics.
The study, titled “Mapping the Genetic Landscape of Treatable Inherited Metabolic Disorders in a Large Middle Eastern Biobank”, was recognized with the journal’s Editor’s Choice Award.
Inherited Metabolic Disorders (IMDs) are rare conditions caused by enzyme deficiencies rooted in genetic abnormalities that disrupt the body’s metabolism. While individual cases are uncommon, the collective prevalence is significant, estimated at one in 2,500 to 5,000 live births.
Conducted in collaboration with the Qatar Precision Health Institute (QPHI), the study was led by Dr. Khalid Fakhro, Chief Research Officer, and first authored by Dr. Geethanjali Devadoss Gandhi, Senior Postdoctoral Fellow at Sidra Medicine. The research analyzed genome sequencing data from over 14,000 participants in QPHI, focusing on 125 genes linked to 115 treatable IMDs.
“Our study addresses a critical gap by focusing on the Qatari population, which has been underrepresented in previous genomic datasets,” said Prof. Khalid Fakhro. “Through our analysis of QPHI data, we identified 69 treatable IMDs within the Qatari population. Understanding the prevalence of these metabolic disorders through genetic carrier and newborn screenings, especially in regions with high rates of consanguinity, provides a robust methodology for future research in population biobanks.”
The study revealed a notable carrier frequency and disease burden for 46 treatable IMDs in Qatar. Approximately one in 13 unrelated individuals (8%) were carriers of at least one IMD, with 31 participants (0.2%) carrying multiple disease-causing variants. Disorders such as phenylketonuria (PKU)/hyperphenylalaninemia and homocystinuria were found to have particularly high carrier frequencies—one in 68 and one in 85, respectively.
The estimated disease burden in the population was calculated at one in 5,038 for PKU/hyperphenylalaninemia and one in 6,315 for homocystinuria.
Dr. Geethanjali Devadoss Gandhi commented, “Our findings are especially significant given the lack of data on PKU/hyperphenylalaninemia prevalence among Qataris. This underscores the urgent need for comprehensive research on treatable inherited metabolic disorders. We are hopeful that this research will pave the way for new treatment options to address previously unrecognized health challenges in Qatar.”
Dr. Ammira Al-Shabeeb Akil, Principal Investigator and lead of the Genetics and Metabolic Clinical Research Program, emphasized the broader implications: “Our study highlights the importance of large-scale population screenings across the MENA region. This will enable precision medicine therapies tailored to specific populations. Collaborations like the Newborn Genome Screening Research Programme with Hamad Medical Corporation will facilitate the early diagnosis of genetic conditions in newborns within Qatar’s general population.”
The study was also awarded first place for its abstract presentation at the MENA Congress for Rare Diseases 2024 in Abu Dhabi, underscoring its significant impact on Arab populations.
