Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, No.5 Fu-Hsing St. Kuei Shan Hsiang, Taoyuan, Taoyuan Hsien, Taiwan.
Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Pediatr Rheumatol Online J. 2022 Aug 13;20(1):68. doi: 10.1186/s12969-022-00722-6.
Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5.
Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy.
Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.
红斑狼疮（SLE）很少在 5 岁之前被诊断出来。那些在很小的时候就发病的患者具有更高的遗传风险和更严重的表型。我们对满足 2012 年 SLICC SLE 分类标准且发病年龄小于 5 岁的患者进行了全外显子组测序，以调查其遗传病因和临床表现。
在台湾一家三级医疗中心定期随访的 184 例儿童发病的 SLE 患者中，有 7 例（3.8%）发病年龄≦5 岁，进行了特征性回顾和基因分析。与发病年龄较大的患者相比，发病年龄在 5 岁之前的患者更有可能患有增生性肾小球肾炎、肾血栓性微血管病、神经精神障碍和生长迟缓。在 3 例患者中确定了致病遗传病因。除了大量自身抗体外，TREX1（c.292_293 ins A）突变纯合子患者还表现出冻疮样皮肤损伤、周围性痉挛、内分泌失调，并经历了多次侵袭性感染。SLC7A7（c.625 + 1 G > A）突变患者患有严重的肾小球肾炎，伴有全肾小球沉积以及高氨血症、代谢性酸中毒和间歇性意识障碍。另外两例患者携带狼疮相关基因 C1s、C2、DNASE1 和 DNASE1L3 以及 CFHR4 的变异。尽管这些患者符合狼疮的分类标准，但许多患者需要超出常规治疗的治疗。
在怀疑患有早发性 SLE 的患者中，发现了相当一部分患者存在遗传病因和狼疮模拟物。详细的临床评估和基因检测对于定制护理和个性化治疗很重要。
