AUTHOR=Alfadhel Majid , Almuqbil Mohammed , Al Mutairi Fuad , Umair Muhammad , Almannai Mohammed , Alghamdi Malak , Althiyab Hamad , Albarakati Rayyan , Bashiri Fahad A. , Alshuaibi Walaa , Ba-Armah Duaa , Saleh Mohammed A. , Al-Asmari Ali , Faqeih Eissa , Altuwaijri Waleed , Al-Rumayyan Ahmed , Balwi Mohammed Ali , Ababneh Faroug , Alswaid Abdulrahman Faiz , Eyaid Wafaa M. , Almontashiri Naif A. M. , Alhashem Amal , Hundallah Khalid , Bertoli-Avella Aida , Bauer Peter , Beetz Christian , Alrifai Muhammad Talal , Alfares Ahmed , Tabarki Brahim 

TITLE=The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.633385

DOI=10.3389/fped.2021.633385

ISSN=2296-2360

ABSTRACT=Background: Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs. 
Methods: We conducted a retrospective chart review of a consecutive series of patients diagnosed with different types of LD from four large tertiary referral centers in Riyadh, Saudi Arabia. Only those (30 disorders) defined by GLIA as LDs were included. 
Results: In total, 83 children from 61 families were identified and recruited for this study. The male-to-female ratio was 1.5:1, and a consanguinity rate of 58.5% was observed. An estimated prevalence of 1:48780 or 2.05/100000 was observed based on the clinical cohort, whereas a minimum of 1:32857 or 3.04/100000 was observed based on the local genetic database. The central region of the country exhibited the highest prevalence of LDs (48.5%). The most common LD was metachromatic leukodystrophy (MLD), where it accounted for 25.3%, The most common disorder based on carrier frequency was AGSNovel variants were discovered in 51% of the cases, but 49% possessed previously reported variants. Missense variants were high in number and accounted for 73% of all cases. Compared to other disorders, MLD due to saposin b deficiency was more common than expected, Pelizaeus-Merzbacher-like disease was more prevalent than Pelizaeus-Merzbacher disease, and X-linked adrenoleukodystrophy was less common than expected. The mortality rate among our patients with LD was 24%.
Conclusion: To the best of our knowledge, this is the largest cohort of patients with LD from Saudi Arabia. We present epidemiological, clinical, radiological, and genetic data. Furthermore, we report 18 variants that have not been reported previously. These findings are of great clinical and molecular utility for diagnosing and managing patients with LD.