The Genetic Landscape of Pompe Disease in the Middle East, North Africa, and Turkey (MENAT Region): A Systematic Review of GAA Variants and Genotype–Phenotype Correlation

Pompe disease is a rare autosomal recessive multisystem disorder caused by pathogenic variants in the acid alpha-glucosidase (GAA) gene, resulting in lysosomal glycogen accumulation and a broad clinical spectrum ranging from rapidly fatal infantile-onset disease (IOPD) to slowly progressive late-onset Pompe disease (LOPD). The genetic epidemiology of Pompe disease across the Middle East, North Africa, and Turkey (MENAT) region remains poorly characterized despite high regional rates of consanguinity. We systematically searched PubMed, ScienceDirect, Google Scholar, and Scopus from inception to July 2026 for studies reporting GAA variants in patients with Pompe disease from MENAT countries, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included 24 studies comprising 134 patients with Pompe disease, identifying 61 distinct GAA variants. Twelve variants were unique to the MENAT region. Missense variants were the most common variant type, accounting for 50.8% of all distinct variants, followed by frameshift variants 19.7%. Egypt contributed the largest number of reported patients (24/134, 17.9%) followed by Saudi Arabia, Iran, and Iraq (18/134, 13.4%) for each country. The most prevalent variant across the MENAT region is the leaky intronic splice-site variant c.-32-13T>G, reported in 11.2% of all patients and in cases from Turkey, Algeria, Iran and Egypt. Of the 61 distinct variants, 35 were associated with IOPD and 24 with LOPD, with c.1064T>C (p.Leu355Pro) and c.2104C>T (p.Arg702Cys) reported in association with both phenotypes. This systematic review identified country-specific variants in the MENAT region related to Pompe disease that are distinct from other reported variants worldwide. Further studies with larger sample sizes are needed to comprehend the genotype–phenotype correlation for Pompe disease in the MENAT region.