Tian Qiu-Ju, Zhang Lu-Jia, Zhang Qun, Liu Feng-Chao, Xie Man, Cai Jin-Zhen, Rao Wei
Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China.
Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China.
World J Gastroenterol. 2025 May 7;31(17):105347. doi: 10.3748/wjg.v31.i17.105347.
Protein-losing enteropathy (PLE) is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia. Patients with Noonan syndrome may present with disorder of lymph vessel formation. However, PLE is rarely reported with Noonan syndrome.
A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia. Additional manifestations included a ventricular septal defect at birth, intermuscular hemangioma, slightly wide interocular and intermammary distances, and absence of the distal phalanx of the left little finger since birth. Abdominal computed tomography revealed cavernous transformation of the portal vein, and liver biopsy indicated "porto-sinusoidal vascular disease". Whole exome and Sanger sequencing revealed a heterozygous mutation (exon9: C.850C>T:P.R284C) in leucine zipper-like transcription regulator 1, suggesting Noonan syndrome type 10. Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient. A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction. Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction, the patient achieved persistent normal serum albumin level without edema or diarrhea. Furthermore, the relevant literatures on Noonan syndrome and PLE were reviewed.
Herein, we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1 (c.850C>T:P.R284C) with newly reported manifestations. This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia, intestinal lymphangiectasia and PLE.
蛋白丢失性肠病（PLE）是低白蛋白血症的一种罕见病因，可归因于肠道淋巴管扩张症。努南综合征患者可能出现淋巴管形成障碍。然而，努南综合征合并PLE的报道很少。
一名15岁女性因低白蛋白血症继发反复水肿和腹泻多次住院。其他表现包括出生时室间隔缺损、肌间血管瘤、眼间距和乳间距略宽，以及自出生以来左手小指远节指骨缺如。腹部计算机断层扫描显示门静脉海绵样变性，肝脏活检提示“门静脉-肝窦血管病”。全外显子组测序和桑格测序显示亮氨酸拉链样转录调节因子1存在杂合突变（外显子9：c.850C>T:p.R284C），提示10型努南综合征。进一步检查发现该患者存在胸导管发育异常和肠道淋巴管扩张症导致PLE。多学科团队决定解决胸导管发育异常伴出口梗阻的问题。胸导管出口梗阻显微手术解除约两年后，患者血清白蛋白水平持续正常，无水肿或腹泻。此外，还对努南综合征和PLE的相关文献进行了综述。
在此，我们报告了首例由亮氨酸拉链样转录调节因子1（c.850C>T:p.R284C）罕见基因突变引起的与努南综合征相关的PLE病例，并伴有新报道的临床表现。该病例成功治疗了因胸导管发育异常、肠道淋巴管扩张症和PLE导致的临床低白蛋白血症。
