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

Autor:	Alfadhel M; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia.; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Almuqbil M; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Division of Neurology, Department of Pediatrics, King Abdullah Specialist Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Al Mutairi F; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Umair M; Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia., Almannai M; Section of Medical Genetics, Children's Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Alghamdi M; Medical Genetics Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Althiyab H; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Albarakati R; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Bashiri FA; Division of Neurology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Alshuaibi W; Medical Genetics Division, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Ba-Armah D; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Division of Neurology, Department of Pediatrics, King Abdullah Specialist Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Saleh MA; Section of Medical Genetics, Children's Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Al-Asmari A; Section of Medical Genetics, Children's Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Faqeih E; Section of Medical Genetics, Children's Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Altuwaijri W; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Division of Neurology, Department of Pediatrics, King Abdullah Specialist Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Al-Rumayyan A; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Division of Neurology, Department of Pediatrics, King Abdullah Specialist Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Balwi MA; Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH), Riyadh, Saudi Arabia.; Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia., Ababneh F; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Alswaid AF; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Eyaid WM; Division of Medical Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Almontashiri NAM; Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunwarah, Saudi Arabia.; Faculty of Applied Medical Sciences, Taibah University, Almadinah Almunwarah, Saudi Arabia., Alhashem A; Division of Genetics, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Hundallah K; Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Bertoli-Avella A; CENTOGENE AG, Rostock, Germany., Bauer P; CENTOGENE AG, Rostock, Germany., Beetz C; CENTOGENE AG, Rostock, Germany., Alrifai MT; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.; Division of Neurology, Department of Pediatrics, King Abdullah Specialist Children's Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia., Alfares A; Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia.; Department of Pediatrics, Almulyda, Saudi Arabia. King Abdullah International Medical Research Center (KAIMRC), Qassim University, Riyadh, Saudi Arabia., Tabarki B; Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Jazyk:	angličtina
Zdroj:	Frontiers in pediatrics [Front Pediatr] 2021 May 13; Vol. 9, pp. 633385. Date of Electronic Publication: 2021 May 13 (Print Publication: 2021).
DOI:	10.3389/fped.2021.633385
Abstrakt:	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 1:48,780 or 2.05/100,000 was observed based on the clinical cohort, whereas a minimum of 1:32,857 or 3.04/100,000 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), and it accounted for 25.3%. The most common disorder based on carrier frequency was AGS. Novel 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 with 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Alfadhel, Almuqbil, Al Mutairi, Umair, Almannai, Alghamdi, Althiyab, Albarakati, Bashiri, Alshuaibi, Ba-Armah, Saleh, Al-Asmari, Faqeih, Altuwaijri, Al-Rumayyan, Balwi, Ababneh, Alswaid, Eyaid, Almontashiri, Alhashem, Hundallah, Bertoli-Avella, Bauer, Beetz, Alrifai, Alfares and Tabarki.)
Databáze:	MEDLINE
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