Zhang Huiting, Zhang Jingtao, Ma Weimeng, Ma Xue, He Ruxuan, Ding Yuan, Liu Yupeng, Zhang Wenyue, Dong Hui, Zhang Yao, He Miao, Yang Yanling
Children's Medical Center, Peking University First Hospital, Beijing 102600, China.
Department of Respiration, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Mol Genet Metab. 2025 Aug;145(4):109178. doi: 10.1016/j.ymgme.2025.109178. Epub 2025 Jun 15.
The most common congenital disorders of glycosylation (CDG) is the phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG). PMM2-CDG is a complex genetic disorder that often found in infancy or early childhood with a clinically heterogeneous variety of neurological and non- neurological symptoms. To expand the phenotypic and genetic spectrum of PMM2-CDG, we summarized the characteristics of 20 Chinese patients.
All patients were diagnosed by genetic analysis. Clinical characteristics, genotypes, imaging, electrophysiological, and metabolic data were analyzed retrospectively.
Twelve males and eight females with PMM2-CDG were included. The median age at diagnosis was 12.0 (ranging from 6.0 to 52.0) months, while the median age at final follow-up was 10.3 (ranging from 5.1 to 12.8) years. All patients exhibited multisystem symptoms and various neurological symptoms were observed. Developmental delay was the primary initial symptoms. Dystaxia, growth retardation and liver damage were also common phenotypes. Cerebellar atrophy was the characteristic abnormality on brain imaging. Fourteen variants of the PMM2 gene were identified, of which five, c.82A > G (p.M28V), c.551C > T (p. P184L), c.640G > T (p.G214C), c.656A > T (p.E219V) and c.712C > G (p.R238G), were newly reported. The most prevalent variant was c.430 T > C (p.F144L), which was identified in 65.0 % of patients, followed by c.395 T > C (p.I132T). Consistent with reports from other populations, missense variants constituted the predominant type of PMM2 gene alterations.
PMM2-CDG presents as a multi-system disease with diverse clinical phenotypes, posing challenges to early identification and diagnosis. The most common pathogenic variant in this Chinese cohort was c.430 T > C (p.F144L), which is close to, but different from, the common pathogenic variant c.422G > A (p.R141H) among European PMM2-CDG patients.
最常见的糖基化先天性疾病（CDG）是磷酸甘露糖变位酶2（PMM2）缺乏症（PMM2-CDG）。PMM2-CDG是一种复杂的遗传性疾病，常在婴儿期或幼儿期发病，具有临床上多种多样的神经和非神经症状。为了扩大PMM2-CDG的表型和基因谱，我们总结了20例中国患者的特征。
所有患者均通过基因分析确诊。对临床特征、基因型、影像学、电生理和代谢数据进行回顾性分析。
纳入12例男性和8例女性PMM2-CDG患者。诊断时的中位年龄为12.0（范围6.0至52.0）个月，而末次随访时的中位年龄为10.3（范围5.1至12.8）岁。所有患者均表现出多系统症状，并观察到各种神经症状。发育迟缓是主要的初始症状。共济失调、生长发育迟缓及肝损害也是常见的表型。小脑萎缩是脑部影像学的特征性异常。共鉴定出PMM2基因的14种变异，其中5种，即c.82A>G（p.M28V）、c.551C>T（p.P184L）、c.640G>T（p.G214C）、c.656A>T（p.E219V）和c.712C>G（p.R238G）为新报道的变异。最常见的变异是c.430T>C（p.F144L），在65.0%的患者中被鉴定出，其次是c.395T>C（p.I132T）。与其他人群的报道一致，错义变异是PMM2基因改变的主要类型。
PMM2-CDG表现为一种具有多种临床表型的多系统疾病，给早期识别和诊断带来挑战。该中国队列中最常见的致病变异是c.430T>C（p.F144L），与欧洲PMM2-CDG患者中常见的致病变异c.422G>A（p.R141H）相近但不同。
