Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.
Mod Rheumatol Case Rep. 2024 Jul 8;8(2):280-285. doi: 10.1093/mrcr/rxae004.
Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto's thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.
努南综合征（Noonan syndrome，NS）是一种常染色体显性遗传性疾病，其基因突变可导致鼠肉瘤病毒/丝裂原活化蛋白激酶通路的组成成分或调节因子异常。其诊断主要依据特征性表现，包括典型的面部特征、身材矮小、先天性心脏病、轻度发育迟缓及隐睾。NS 患者有时会并发自身免疫性疾病，如桥本甲状腺炎，极少数情况下还会并发系统性红斑狼疮（systemic lupus erythematosus，SLE）。本文报道了 1 例 29 岁日本女性 NS 并发 SLE 和反复严重低血糖的病例。该患者根据血小板减少、肾炎、抗核抗体滴度阳性（1:640）和抗双链 DNA 抗体阳性而被诊断为 SLE。患者接受了糖皮质激素、霉酚酸酯和他克莫司治疗，这既改善了 SLE，又缓解了低血糖。由于胰岛素受体抗体水平高于正常上限，且治疗后降低，因此低血糖可能归因于 B 型胰岛素抵抗综合征。本文报道了首例 NS 并发 B 型胰岛素抵抗综合征的 SLE 病例。虽然 NS 是一种罕见疾病，但我们需要考虑到包括 SLE 在内的自身免疫性疾病的并发症。
