Journal
JOURNAL OF INTERNAL MEDICINE
Volume 290, Issue 1, Pages 129-140Publisher
WILEY
DOI: 10.1111/joim.13224
Keywords
colitis; Hermansky-Pudlak syndrome; inflammatory bowel disease; infliximab; tumor necrosis factor alpha
Categories
Funding
- National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases
- Office of the Director, National Institutes of Health, Bethesda, Maryland
- National Cancer Institute
- NIH/NCI [P30-CA051008]
Ask authors/readers for more resources
This study aimed to expand the understanding of IBD in patients with Hermsnky-Pudlak syndrome (HPS) by retrospectively analyzing records and clinical features of patients evaluated at the NIH Clinical Center. Results showed that some patients with HPS develop IBD resembling Crohn's disease, with genetic heterogeneity being a feature of HPS IBD. The study also identified HPS3 as a new gene associated with human IBD, and early-onset IBD can occur in patients with HPS.
Background. Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective. To expand the understanding of IBD in patients with HPS. Methods. Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results. IBD affected 37 (14.2%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions. IBD resembling Crohn's disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available