Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

脑白质营养不良（LD）是一组异质性进行性神经系统疾病，其特征是主要累及中枢神经系统（CNS）的白质。这是伊朗 LD 登记数据库第一份描述波斯脑白质营养不良患者的临床、放射学和基因组数据的报告。从 2016 年到 2019 年，对怀疑患有 LD 的患者进行了检查，随后进行了脑部磁共振成像 (MRI)。根据神经放射学表型使用单基因测试或全外显子组测序（WES）。在少数情况下，诊断是通过代谢研究做出的。根据 MRI 模式，诊断患者被分为 A 组（髓鞘形成低下 LD）和 B 组（其他 LD）。采用最新的 LD 分类对诊断患者进行分类。对于新的变异，进行了计算机分析以验证其致病性。在 680 名注册患者中，342 名完成了诊断评估。总共有 245 名患者得到了诊断，其中 24.5% 被归类为 A 组，其余的被归类为 B 组。基因测试揭示了 228 名患者的因果变异，其中包括 110 个基因的 213 个变异和 78 个新变异。WES 和单基因测试分别在 65.5% 和 34.5% 的病例中发现了致病变异。WES总诊断率为60.7%。溶酶体疾病（27.3%；GM2-神经节苷脂沉积症-9.8%，MLD-6.1%，KD-4.5%），氨基酸和有机酸疾病（17.15%；卡纳万病-4.5%，L-2-HGA-3.6%），线粒体脑白质营养不良 (12.6%)、离子和水稳态紊乱 (7.3%; MLC-4.5%)、过氧化物酶体疾病 (6.5%; X-ALD-3.6%) 和髓鞘蛋白紊乱 (3.6%; PMLD-3.6%) 是最常诊断的疾病。37% 的病例在 9 个基因（ARSA、HEXA、ASPA、MLC1、GALC、GJC2、ABCD1、L2HGDH、GCDH）中存在致病性变异。这项研究强调了伊朗儿童 LD 的最常见类型以及遗传异质性。