The landscape of pediatric genetic white matter disorders at a tertiary referral hospital in Upper Egypt and the report of 31 novel variants

Abstract

Background: Leukodystrophies (LDs) and genetic leukoencephalopathies (GLEs) encompass the spectrum of genetic white matter disorders (GWMDs). Despite their clinical significance, limited studies have investigated GWMDs in Egypt. Therefore, this study aimed to characterize pediatric patients diagnosed with GWMDs in the Beni-Suef Governorate, Upper Egypt. Methods: We reviewed the records of patients diagnosed with GWMDs who presented over five years to the pediatric neurology clinic of a tertiary care hospital in Beni-Suef Governorate, Upper Egypt. The study included 142 patients aged < 18 years diagnosed with GWMD confirmed by brain imaging, metabolic, and/or molecular genetic testing. Patients were classified as LDs or GLEs per the 2015 Global Leukodystrophy Initiative Consortium (GLIA) criteria. Results: Fifty-six cases were identified to have LDs, while 86 were classified as GLEs. Metachromatic leukodystrophy (MLD) was the most common LD (13 patients), followed by megalencephalic leukoencephalopathy with subcortical cysts (MLC) (10 patients). The most common GLEs were lysosomal storage disorders (LSDs) (22 patients,) followed by Cockayne syndrome (11 patients), along with other miscellaneous disorders. The cumulative incidence of GWMDs in children under 18 was estimated at 10.8 cases per 100,000 population during the five-year study period. Thirty-one novel variants were identified, comprising 10 for LDs and 21 for GLEs. The mortality rate was 39.3% and 22.1% among patients with LDs and GLEs, respectively. Conclusions: This study presents the first cohort of GWMDs reported from the Beni-Suef Governorate, Upper Egypt. The study provides significant data regarding regional etiological patterns, clinical trajectories, and molecular profiles. Additionally, the study findings provide a foundational framework for establishing a national GWMD registry and inform future diagnostic and therapeutic strategies.