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
8 affiliations
- 1Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia
- 2Department of Medicine, Kerry University Hospital, Rathass, V92 NX94 Tralee, Ireland
- 3Clinical Biochemistry Department, Faculty of Medicine, Rabigh Branch, King Abdulaziz University, Rabigh 21911, Saudi Arabia
- 4Department of Physiology, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia
- 5Department of Biomedical Sciences, College of Medicine, King Faisal University, Al Hofuf 36361, Saudi Arabia
- 6Department of Internal Medicine, King Khalid Hospital, Hail 55421, Saudi Arabia
- 7Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia
- 8Department of Pathology, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia
Abstract
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.
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BibTeX
@article{alantry2026genetic,
title = {{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}},
author = {Ahmed Kaid Alantry and Sara Z. Hamdan and Eman A. Kubbara and Mohamad Y. Rezk and Ahmed Mohamedain and Ensherah Hassan Salih Mohamedain and Yousif R. Makki and Ebtihal Kamal and Hamdan Z. Hamdan},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209227},
url = {https://www.mdpi.com/1422-0067/27/20/9227},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Ahmed Kaid Alantry
AU - Sara Z. Hamdan
AU - Eman A. Kubbara
AU - Mohamad Y. Rezk
AU - Ahmed Mohamedain
AU - Ensherah Hassan Salih Mohamedain
AU - Yousif R. Makki
AU - Ebtihal Kamal
AU - Hamdan Z. Hamdan
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209227
UR - https://www.mdpi.com/1422-0067/27/20/9227
AB - 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.
SN - 1422-0067
ER -