患儿，男，足月儿，生后因肤色苍白30 min，呼吸困难10 min入院。体格检查示肤色苍白，眼距宽，耳位低，颈部可触及囊性包块，肝大，右拇指连接球状赘生物，右足第2足趾趾甲异位。入院后查血红蛋白44 g/L，骨髓增生减低，全外显子组测序显示患儿RPS19基因存在c.175T>C（p.Ser59Pro）杂合致病变异，该患儿明确诊断为Diamond-Blackfan贫血。随访至2岁2个月，血红蛋白及网织红细胞计数处于正常水平。该患儿起病早、贫血程度重，其症状丰富了临床疾病谱，为临床诊疗提供思路。

A male full-term neonate was admitted at 30 minutes of life with pallor and 10 minutes of respiratory distress. Physical examination revealed pallor, increased intercanthal distance, low-set ears, a palpable cystic mass in the neck, hepatomegaly, a pedunculated, globular appendage attached to the right thumb, and an ectopic toenail on the right second toe. Laboratory testing showed severe anemia with hemoglobin of 44 g/L. Bone marrow examination demonstrated hypoplasia. Whole-exome sequencing identified a heterozygous pathogenic variant in the RPS19 gene, c.175T>C (p.Ser59Pro), establishing the diagnosis of Diamond-Blackfan anemia. On follow-up to 2 years and 2 months of age, both hemoglobin and reticulocyte counts remained within normal ranges. This case illustrates early-onset severe anemia in a neonate with genetically confirmed Diamond-Blackfan anemia and expands the phenotypic spectrum, informing clinical recognition and management.