探讨Majeed综合征(MS)患儿临床特征和基因变异特点。

选择2022年7月于新疆医科大学附属第一医院诊治的1例MS患儿(患儿1)为研究对象。对其临床病例资料进行回顾性分析，并对国内外数据库中关于MS患者相关研究文献进行检索，分析该病患者的临床特征、遗传学特征及治疗转归。患儿1及其监护人对诊治均知情同意。

①患儿1，女性，14.7岁，反复全身多处关节疼痛12^＋年，伴生长发育落后，身材矮小(身高为129 cm)，偶有发热。对其实验室检查结果显示，红细胞计数及血红蛋白(Hb)水平均降低，红细胞沉降率升高，白细胞介素(IL)-6水平升高；双骶髂＋双膝MRI检查结果显示双下肢大关节骨干骺端炎症表现。患儿1被临床初诊为"全身型幼年型特发性关节炎(JIA)待排"，对其采取糖皮质激素治疗，后调整为糖皮质激素＋甲氨蝶呤/甲氨蝶呤＋阿达木单抗治疗的疗效均欠佳。对患儿1进行全外显子组测序(WES)发现其LPIN2基因Exon20 c．2585C>G(p.Pro862Arg)纯合突变，而被确诊为MS。结合患儿1多次细胞因子检测提示IL-6水平升高，故给予IL-6抑制剂托珠单抗治疗，随访6个月后，患儿1关节疼痛明显缓解，末次随访时，其身高为140.0 cm。②文献复习结果：国内外共检索到MS患者相关研究文献共计16篇，含患儿1在内，共计40例MS患者纳入本研究分析。其中，MS成年患者为3例，儿童为37例；男性与女性比例为23∶13，另外4例性别不详；患者来自7个国家，主要集中于亚洲国家。报道父母是否近亲关系的30例患儿中，23例MS患儿的父母为近亲结婚，包括中国1例(患儿1)及国外22例(73.3%，22/30)MS患儿的父母。这40例MS患者的主要临床表现前4位依次为，先天性红细胞生成障碍性贫血(CDA)占比为97.5%(39/40)，慢性复发性多灶性骨髓炎(CRMO)为95.0%(38/40)，反复发热为67.5%(27/40)，生长发育迟缓为62.5%(25/40)；共发现LPIN2基因突变类型>24种；对MS患者采取生物制剂，如IL-1抑制剂治疗的疗效良好。

MS是一种罕见的常染色体隐性遗传病，早期对患儿进行基因检测有助于该病确诊、降低误诊发生，并可及时对其采取个体化治疗措施，从而降低该病对患儿生长速度与骨骼发育的影响。

To explore the clinical characteristics and genetic variation features of children with Majeed syndrome (MS).

One child with MS (patient 1) diagnosed and treated in the First Affiliated Hospital of Xinjiang Medical University in July 2022 was selected as the study subject. A retrospective analysis of her clinical case data was conducted. Relevant research literature on MS patients in domestic and international databases was retrieved, and the clinical features, genetic characteristics, and treatment outcomes of these patients were analyzed. Patient 1 and her guardians were informed consent for the diagnosis and treatment.

① Patient 1 was a 14.7-year-old female with a history of recurrent multi-joint pain for over 12 years, accompanied by growth retardation, short stature (height 129 cm), and occasional fever. Laboratory findings indicated low red blood cell count and hemoglobin (Hb) level, high erythrocyte sedimentation rate, and elevated interleukin (IL)-6 levels. MRI of bilateral sacroiliac joints and knees showed inflammatory changes in the metaphyses of the large joints of the lower limbs. Patient 1 was initially diagnosed as ＂systemic juvenile idiopathic arthritis (JIA) to be ruled out＂, and was treated with glucocorticoids, later adjusted to glucocorticoids + methotrexate / methotrexate + adalimumab, all with poor efficacy. Whole-exome sequencing (WES) of patient 1 revealed a homozygous mutation in the LPIN2 gene [Exon20 c. 2585C>G (p.Pro862Arg)], and confirming the diagnosis of MS. Based on repeated cytokine tests showing high IL-6 levels, the IL-6 inhibitor tocilizumab was administered. After 6 months of follow-up, her joint pain significantly improved, and her height at the last follow-up was 140.0 cm. ② Literature review results: a total of 16 relevant research articles on MS patients were retrieved globally, including patient 1, encompassing 40 MS patients for analysis. Among them, 3 were adults and 37 were children; the ratio of males to females was 23∶13, with 4 cases of unknown gender; all cases were reported from 7 countries, mainly concentrated in Asia. Among the 30 cases reporting parental consanguinity, 23 had consanguineous parents, including 1 case from China (patient 1) and 22 cases (73.3%, 22/30) from other countries. The top four clinical manifestations of 40 patients were congenital dyserythropoietic anemia (CDA) accounted for 97.5% (39/40), chronic recurrent multifocal osteomyelitis (CRMO) accounted for 95.0% (38/40), recurrent fever accounted for 67.5% (27/40), and growth retardation accounted for 62.5% (25/40). At least 24 pathogenic LPIN2 gene mutations were identified. Biologics, such as IL-1 inhibitors, showed good efficacy.

MS is a rare autosomal recessive genetic disorder. Early genetic testing helps confirm the diagnosis of MS, reduce misdiagnosis, and enable timely personalized treatment to mitigate the impact on the child′s growth velocity and skeletal development.