Gragnaniello Vincenza, Cazzorla Chiara, Gueraldi Daniela, Puma Andrea, Loro Christian, Burlina Alberto B
Division of Inherited Metabolic Diseases, Department of Women's and Children's Health, University Hospital of Padova, 35128 Padova, Italy.
Metabolites. 2025 May 29;15(6):361. doi: 10.3390/metabo15060361.
Lysosomal storage disorders (LSDs) are rare inherited metabolic diseases characterized by defects in lysosomal enzyme function or membrane transport. These defects lead to substrate accumulation and multisystemic manifestations. This review focuses on gastrointestinal (GI) involvement in LSDs, which is a significant but often overlooked aspect of these disorders.
A comprehensive literature review was conducted to examine the pathophysiology, clinical presentation, diagnosis and management of GI manifestations in several LSDs, including Fabry disease, Gaucher disease, Pompe disease, Niemann-Pick disease type C, mucopolysaccharidoses and Wolman disease.
The pathogenesis of GI involvement in LSDs varies and encompasses substrate accumulation in enterocytes, mesenteric lymphadenopathy, mass effects, smooth muscle dysfunction, vasculopathy, neuropathy, inflammation and alterations to the microbiota. Clinical presentations range from non-specific symptoms, such as abdominal pain, diarrhea and malabsorption, to more severe complications, such as protein-losing enteropathy and inflammatory bowel disease. Diagnosis often requires a high level of suspicion, as GI symptoms may precede the diagnosis of the underlying LSD or be misattributed to more common conditions. Management strategies include disease-specific treatments, such as enzyme replacement therapy or substrate reduction therapy, as well as supportive care and targeted interventions for specific GI complications.
This review highlights the importance of recognizing and properly managing GI manifestations in LSDs to improve patient outcomes and quality of life. It also emphasizes the need for further research to develop more effective treatments for life-threatening GI complications associated with these rare genetic disorders.
溶酶体贮积症（LSDs）是罕见的遗传性代谢疾病，其特征为溶酶体酶功能或膜转运缺陷。这些缺陷导致底物蓄积和多系统表现。本综述聚焦于LSDs的胃肠道（GI）受累情况，这是这些疾病的一个重要但常被忽视的方面。
进行了一项全面的文献综述，以研究几种LSDs（包括法布里病、戈谢病、庞贝病、尼曼-皮克病C型、黏多糖贮积症和沃尔曼病）中GI表现的病理生理学、临床表现、诊断和管理。
LSDs中GI受累的发病机制各不相同，包括肠细胞内底物蓄积、肠系膜淋巴结病、占位效应、平滑肌功能障碍、血管病变、神经病变、炎症以及微生物群改变。临床表现从非特异性症状，如腹痛、腹泻和吸收不良，到更严重的并发症，如蛋白丢失性肠病和炎症性肠病。诊断通常需要高度怀疑，因为GI症状可能在潜在LSD诊断之前出现，或者被误诊为更常见的疾病。管理策略包括针对疾病的治疗，如酶替代疗法或底物减少疗法，以及针对特定GI并发症的支持性护理和靶向干预。
本综述强调了认识和妥善管理LSDs中GI表现对于改善患者预后和生活质量的重要性。它还强调需要进一步研究，以开发针对这些罕见遗传疾病相关的危及生命的GI并发症的更有效治疗方法。
