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      Urinary glutamine/glutamate ratio as a potential biomarker of pediatric chronic intestinal pseudo-obstruction

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          Abstract

          Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other gastrointestinal diseases like short bowel syndrome (SBS). Therefore, it is desirable to identify and establish new laboratory diagnostic markers for CIPO that are reliable and easily accessible. In our study we have identified the ratio of the urinary glutamine and glutamic acid as a promising biomarker for distinguishing suspected CIPO cases and simple SBS cases. The area under ROC curve was 0.83, at cutoff value = 7.04 with sensitivity of 65% and specificity of 92%.

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          The online version of this article (doi:10.1186/s13023-017-0615-3) contains supplementary material, which is available to authorized users.

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          Chronic intestinal pseudo-obstruction.

          Joseph Gabbard, Brian E. Lacy (2013)
          Chronic intestinal pseudo-obstruction (CIP) is a rare and serious disorder of the gastrointestinal (GI) tract characterized as a motility disorder with the primary defect of impaired peristalsis; symptoms are consistent with a bowel obstruction, although mechanical obstruction cannot be identified. CIP is classified as a neuropathy, myopathy, or mesenchymopathy; it is a neuropathic process in the majority of patients. The natural history of CIP is generally that of a progressive disorder, although occasional patients with secondary CIP note significant symptomatic improvement when the underlying disorder is identified and treated. Symptoms vary from patient to patient depending on the location of the luminal GI tract involved and the degree of involvement; however, the small intestine is nearly always involved. Common symptoms include dysphagia, gastroesophageal reflux, abdominal pain, nausea, vomiting, bloating, abdominal distension, constipation or diarrhea, and involuntary weight loss. Unfortunately, these symptoms are nonspecific, which can contribute to misdiagnosis or a delay in diagnosis and treatment. Since many of the symptoms and signs suggest a mechanical bowel obstruction, diagnostic tests typically focus on uncovering a mechanical obstruction, although routine tests do not identify an obstructive process. Nutrition supplementation is required for many patients with CIP due to symptoms of dysphagia, nausea, vomiting, and weight loss. This review discusses the epidemiology, etiology, pathogenesis, diagnosis, and treatment of patients with CIP, with an emphasis on nutrition assessment and treatment options for patients with nutrition compromise.
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            Chronic intestinal pseudo-obstruction syndrome in pediatrics. Results of a national survey by members of the North American Society of Pediatric Gastroenterology and Nutrition.

            Jorge Vargas, Paula Sachs, Marvin Ament (1988)
            A total of 87 cases of chronic intestinal pseudo-obstruction were identified as fitting the criteria for the syndrome. Five families, three with autosomal dominant inheritance, accounted for 15 cases. The remainder were single cases in families, indicating either autosomal recessive inheritance, spontaneous mutation, or acquired disease. Of the 87 patients, 47 were male; 19 patients were symptomatic at birth and 37 (43%) within the first month of life; 64% were diagnosed by the first year of age and the remainder were diagnosed by 18 years of age. Patients currently range in age from 3 months to 24 years. Abdominal distension in 70, vomiting in 50, and constipation in 50 of the 87 cases were the three commonest presenting symptoms. Diarrhea and failure to thrive were present in 20 cases. Urinary tract infection and failure to void were present in 10 cases. Diagnosis was established by clinical presentation, radiographic studies, and at exploratory laparotomy. Esophageal motility was abnormal in 14 patients. Anal manometric studies were done in 16 and showed normal recto-anal inhibitory reflex in all but one. Only 34 patients had biopsy studies as part of their evaluation and, of these, only 12 were full-thickness. Abnormal plexuses were found in eight and degeneration of smooth muscles in four. There was little or no benefit from the use of any medication to promote motility. One patient with intractable pseudo-obstruction benefited from a subtotal enterectomy. Of those patients not lost to follow-up, 31.4% died; 43% of these deaths occurred within the first 6 months from complications of total parenteral nutrition. One infant had a complete spontaneous remission by 1 year of age, with normalization of radiographic findings; another had partial remission by 6 months of age.
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              Long-term outcome of congenital intestinal pseudoobstruction.

              Hayat Mousa, Paul Hyman, Jose Cocjin … (2002)
              We evaluated 85 children with congenital chronic intestinal pseudoobstruction (CIP) over the past 10 years. Twelve (14%) were born prematurely. One had a family history of CIP. Six had systemic diseases. Thirty-five (41%) had urinary bladder involvement. Manometric features were consistent with myopathy in 32, neuropathy in 48, and mixed disease in 5. Of 48 patients with neuropathy, 6 had urinary bladder involvement (12.5%) (P < 0.0001 vs myopathy), and 10 had malrotation (21%) (P = NS vs myopathy). Upon referral, 53 (62%) were dependent on partial or total parenteral nutrition (PN). At the time of chart review (median 25 months after evaluation), 22 patients had died, 14 of whom were on total PN, 13 of them died because of PN-related complications and 1 died of sepsis. Three others died of sepsis while on partial PN (P = 0.007 vs mortality in patients fed enterally) and five died after small bowel transplantation. In conclusion, in children with congenital CIP, the risk for prematurity is increased twofold, the majority of cases are sporadic, abnormal bladder function is more common in myopathic CIP, and complications related to parenteral nutrition are the main cause of death in children with CIP.
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                Author and article information

                Contributors
                Jun-Kai Yan: yanjunkai2015@sjtu.edu.cn
                Ke-Jun Zhou: zhoukejun1984@hotmail.com
                Jian-Hu Huang: hjh19911101@qq.com
                Qing-Qing Wu: 852509291@qq.com
                Tian Zhang: 997856659@qq.com
                Chao-Chen Wang: abelardccwang@gmail.com
                Wei Cai: caiw204@sina.com
                Journal
                Journal ID (nlm-ta): Orphanet J Rare Dis
                Journal ID (iso-abbrev): Orphanet J Rare Dis
                Title: Orphanet Journal of Rare Diseases
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1750-1172
                Publication date (Electronic): 28 March 2017
                Publication date PMC-release: 28 March 2017
                Publication date Collection: 2017
                Volume: 12
                Electronic Location Identifier: 62
                Affiliations
                [1 ]ISNI 0000 0004 0630 1330, GRID grid.412987.1, Department of Pediatric Surgery, , Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, ; 1665 Kongjiang Rd, Shanghai, 200092 China
                [2 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, , Shanghai Institute for Pediatric Research, ; Shanghai, China
                [3 ]Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
                [4 ]ISNI 0000 0001 0727 1557, GRID grid.411234.1, Department of Public Health, , Aichi Medical University, ; Aichi, Japan
                Article
                Publisher ID: 615
                DOI: 10.1186/s13023-017-0615-3
                PMC ID: 5371254
                SO-VID: 11fa6ee2-f482-4649-a95d-92ab5985eeba
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 20 September 2016
                Date accepted : 21 March 2017
                Funding
                Funded by: Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition
                Award ID: 14DZ2272400
                Award Recipient :
                Funded by: Shanghai Municipal Commission of Health and Family Planning
                Award ID: 2013ZYJB0017
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003399, Science and Technology Commission of Shanghai Municipality;
                Award ID: 14411950400/ 14411950401
                Award Recipient :
                Categories
                Subject: Letter to the Editor
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: chronic intestinal pseudo-obstruction,short bowel syndrome,urinary glutamine/glutamate ratios,biomarker
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: chronic intestinal pseudo-obstruction, short bowel syndrome, urinary glutamine/glutamate ratios, biomarker

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