PEDİATRİK YAŞ GRUBUNDA BEYAZ CEVHER HASTALIKLARINDA VERİ TABANI OLUŞTURULMASI

Abstract

Genetic white matter disorders (GWMD) are a group of heterogeneous diseases due to variants in the genes affecting central nervous system white matter. Clinical findings are heterogenous and may present at different age groups. The diagnostic process includes clinical evaluation, neuroimaging, biochemical and genetic tests. Establishing a comprehensive database and registry in pediatric GWMD is the first step to understand the yield of diagnostic pathways. We aimed to centralize clinical, imaging and genetic data by creating a database in this rare disease group and aim to retrospectively review the diagnostic distribution and yield in terms of neuroimaging, biochemical and molecular findings. This retrospective review included patients aged 0- 18 years with white matter lesions on MRI, followed up at Hacettepe University İhsan Doğramacı Children's Hospital Department of Pediatrics, Division of Pediatric Neurology and Department of Radiology between June 2010 and June 2022, Among 237 patients (88 female, 149 male), the mean and median age at the time of admission were 54,35 (±53,11) and 37 (0-221,54) months, respectively. The most common findings were global developmental delay (n= 134, 56,5%), muscle weakness (n= 51, 34,7%) and intellectual disability (n= 77, 32,5%). Among the patients with a definite diagnosis (n= 113; 47.5%), the distribution of diagnoses were X-linked adrenoleukodystrophy (n= 18; 16%), metachromatic leukodystrophy (n= 12; 10,6%), L2-OH glutaric aciduria (n= 11; 9,7%) and glutaric aciduria type 1 (n= 10; 8,8%). A novel homozygous splice site mutation was detected in the DNAJC3 in one patient. The diagnostic rate in whole patient group was 47.6%, while the diagnostic rate in the group that underwent whole exome sequencing (WES) was 67.3%. Although GWMD are a heterogeneous group of diseases, establishing a diagnostic algorithm is essential for a systematic approach enabling early and accurate diagnosis, as well as effective use of resources. The diagnostic rate in GWMD will increase with the use of genetic studies, especially next generation sequencing. The rarity of GWMD, the complexity of the diagnostic process, and the fact that some variants identified in genetic studies have not been previously associated with any disease complicate diagnosis and follow-up of patients. Therefore, establishing national and international registries to enhance data sharing are utmost important.