Development and Validation of the Spanish AzBio Sentence Corpus

Journal Pre-proof “Unusual white-yellowish dots in the colon reveal a rare metabolic disease” Steven F.G. Jeuring, Bas P.M. Verhaegh, Jef Verbeek PII: DOI: Reference: S0016-5085(20)35565-7 https://doi.org/10.1053/j.gastro.2020.12.025 YGAST 63957 To appear in: Gastroenterology Accepted Date: 15 December 2020 Please cite this article as: Jeuring SFG, Verhaegh BPM, Verbeek J, “Unusual white-yellowish dots in the colon reveal a rare metabolic disease”, Gastroenterology (2021), doi: https://doi.org/10.1053/ j.gastro.2020.12.025. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 by the AGA Institute “Unusual white-yellowish dots in the colon reveal a rare metabolic disease” Steven F.G. Jeuring1, Bas P.M. Verhaegh1, Jef Verbeek1,2,3 1 Division of Gastroenterology-Hepatology, Maastricht University Medical Center +, Maastricht, The Netherlands 2 Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium 3 Laboratory of Hepatology, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium -p Conflict of interest: None of the authors have conflicts of interest to declare ro of Corresponding author: Steven F.G. Jeuring, MD, PhD Division of Gastroenterology-Hepatology, Maastricht University Medical Center+ Postbox 5800, 6202 AZ Maastricht, The Netherlands Telephone: +31433875021, e-mail address: [email protected] re Key words: Tangier disease, storage disease, endoscopy Jo ur na lP Word count: 184 words [question] and 335 words [answer] Question: A 33-year old Syrian man, known with thrombocytopenia, was admitted to the emergency room department because of gastrointestinal bleeding with hemodynamic instability. Emergency gastroscopy was normal and subsequent computed tomography angiography revealed the presence of splenomegaly and an intestinal bleeding at the splenic flexure of the colon due to a priory unknown arteriovenous malformation. The malformation was embolized with coils. Four days later, during colonoscopy, the site of prior bleeding was identified and showed a large non-bleeding postembolization ulcer. Coincidentally, the entire colonic mucosa showed numerous tiny white-yellowish ro of dots with a decreased vascular pattern, but without any edema or erythema [Figure 1]. Multiple biopsies were taken and histological examination showed a diffuse infiltration of the mucosa and -p submucosa with foamy macrophages [Figure 2 [H&E stain] and Figure 3 [CD68 stain, highlighting re macrophages]]. Electron microscopy confirmed the presence of foamy macrophages [Figure 4]. lP Histological staining and polymerase chain reaction analyses on T. whipplei and M. tuberculosis were na negative, as were serologic and urinary analyses on schistosomiasis. Jo splenomegaly? ur What is the cause of the white-yellowish mucosal dots in the colon of this patient with concomitant Answer: Foamy macrophages contain lipid material, mainly cholesterol, and are generally seen in atherosclerotic plaques and in some infectious diseases, such as tuberculosis. Additional laboratory assessment on cholesterol values in our patient revealed a low total cholesterol level [34.8 mg/dL, normal 193-248], an undetectable low high density lipoprotein [HDL] [<3.9 mg/dL, normal >3.9], moderately elevated triglyceride level [328 mg/dL, normal 71-172] and low apoprotein A [apoA] [0.06 g/L, normal 0.95-2.10]. Subsequent genetic testing identified a homozygous mutation in the ATP-binding Cassette Transporter A1 [ABCA1] as being the cause of the hypo-alpha-lipoproteinemia, ro of fitting the diagnosis of Tangier disease. Tangier disease is a very rare, autosomal recessive disorder of the lipid metabolism, characterized by -p undetectable low levels of HDL cholesterol.1 Worldwide, approximately only 100 cases have been re reported in literature. The ABCA1 transporter plays a key role in the transport of free cholesterol lP from the cell to apoA-I in the circulation. In Tangier disease, this transport is impaired, resulting in both accumulation of esterified cholesterol in the cell and rapid catabolism of circulating lipid-poor na apoA-I particles, primarily in the kidney, resulting in HDL deficiency. Cholesterol is mainly deposited ur in reticuloendothelial cells [e.g. macrophages]. Therefore, clinical signs of Tangier disease can be Jo found in macrophage-rich tissues, such as tonsils [giving a characteristically orange discoloration], liver and spleen [hepatosplenomegaly and thrombocytopenia] and the colonic mucosa [giving a diffuse white-yellowish dot appearance]. Excessive storage in Schwann cells can result in peripheral neuropathy, which can be the presenting symptom of the disease.2 The deficiency of HDL particles makes patients prone for cardiovascular diseases at young age.3 In the presented case, the presenting symptom [gastrointestinal blood loss due to an arteriovenous malformation] is probably unrelated to the disease, although impaired platelet activation has been described in Tangier disease. The endoscopic finding of the characteristic white-yellowish dots in the colon, together with the presence of splenomegaly, hinted towards a storage disorder and eventually led to the diagnosis of Tangier disease. Prompt recognition enables timely cardiovascular management in order to reduce the corresponding cardiovascular risk. References 1. Rust S, Rosier M, Funke H, et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet. 1999 Aug;22(4):352-5 2. Puntoni M, Sbrana F, Bigazzi F, et al., Tangier disease: epidemiology, pathophysiology, and management. Am J Cardiovasc Drugs. 2012 Oct 1;12(5):303-11 3. Serfaty-Lacrosniere C, Civeira F, Lanzberg A, et al. Homozygous Tangier disease and Jo ur na lP re -p ro of cardiovascular disease. Atherosclerosis. 1994 May;107(1):85-98. of ro -p re lP na ur Jo of ro -p re lP na ur Jo of ro -p re lP na ur Jo of ro -p re lP na ur Jo