Gastrointestinal findings in children with Down syndrome: Is there an early sign for celiac disease?

Abstract

Aim: To investigate the prevalence of celiac disease (CD) among children with Down’s syndrome (DS) and its association with gastrointestinal symptoms and other accompanying diseases.

Methods: The study was consisted of regular trisomy 21 patients who were under follow-up in our department. The age, gender, gastrointestinal symptoms (abdominal pain, constipation, diarrhea, abdominal distension, vomiting, flatulence, and unsatisfactory weight gain/weight loss) and accompanying diseases were recorded. Anti-tissue transglutaminase (anti-tTG) immunoglobulin A (Ig A) levels were analyzed in all cases. Serologically positive patients were referred to a pediatric gastroenterologist for intestinal biopsy.

Results: Totally 98 children with a mean age of 3.2±2.81 years (range: 2-13 years) diagnosed with the DS were included in this study. Among study participants, 46 (46.9%) were female. Among study participants, 3 (3.1%) had positive anti-tTG IgA results and endoscopic biopsies revealed the diagnosis of Marsh type 3b CD in all of them. In correlation analysis, hypothyroidism (p=0.03) and presence of diarrhea (p=0.04) significantly correlated with the CD presence among children with the DS. Diarrhea increased the risk for 1.50 times (0.67-3.34) while hypothyroidism increased the risk for 2.75 times (0.55-13.67) among patients with DS.

Conclusion: Clinicians should be aware of an increased prevalence of CD among patients with DS especially in children with diarrhea and/or hypothyroidism.

Keywords

• Celiac disease,children,Down syndrome

Down sendromlu çocuklarda gastrointestinal bulgular: Çölyak hastalığı için erken bir belirti var mı?

Öz

Amaç: Down sendromlu (DS) çocuklarda çölyak hastalığının (ÇH) sıklığını ve gastrointestinal semptomlar ve eşlik eden diğer hastalıklarla birlikteliğini saptamak.

Yöntemler: Çalışmaya kliniğimizde takip edilen regüler trizomi 21 olan hastalar alındı. Yaş, cinsiyet, gastrointestinal semptomlar (karın ağrısı, kabızlık, diyare, abdominal distansiyon, kusma, şişkinlik ve kilo alımı / kilo kaybı) ve eşlik eden ek hastalıklar kaydedildi. Tüm olgularda anti-doku transglutaminaz (anti-tTG) immünoglobulin A (IgA) düzeyleri analiz edildi. Serolojik olarak pozitif hastalar, bağırsak biyopsisi çocuk gastroenterolojisi tarafından yapıldı.

Bulgular: Çalışmaya yaş ortalaması 3,2 ± 2,81 yıl (2-13 yıl) olan 98 çocuk alındı. Hastaların 46 (% 46,9) kızdı. Hastaların 3'ünde (% 3,1) anti-tTG IgA pozitifliği vardı ve endoskopik biyopsilerin hepsinde Marsh tip 3b ÇH tanısı saptandı. ÇH saptanan DS'lu çocuklarda, korelasyon analizinde, hipotiroidizm (p=0,03) ve diyare (p=0,04)  görülmesi anlamlıydı. DS'lu hastalarda, ishal görülme riski 1,5 kat (0,67-3,34) artarken hipotiroidizm görülme riski 2.75 kat (0.55-13.67) arttırdığı saptandı.

Sonuç: Klinisyenler, DS'li çocuklarda özellikle diyare ve / veya hipotiroidili varlığında Çölyak hastalığı akılda tutulmalıdır.

Anahtar Kelimeler

• Çölyak hastalığı,Down sendromu,çocuk

Kaynakça

1. 1. Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr 2008;55:349-65.
2. 2. Sevinc E, Sevinc N, Akar HH, et al. Plasma glutamine and cystine are decreased and negatively correlated with endomysial antibody in children with celiac disease. Asia Pac J Clin Nutr. 2016;25:452-6.
3. 3. Nenna R, Guandalini S, Popp A, Kurppa K. Coeliac disease. Autoimmune Dis. 2014;2014:623784.
4. 4. Bull MJ. Health supervision for children with Down syndrome. Pediatrics. 2011;128:393-406.
5. 5. Giménez-Barcons M, Casteràs A, Armengol Mdel P, Porta E, Correa PA, Marín A et al. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. J Immunol. 2014;193:3872-9.
6. 6. Bhat AS, Chaturvedi MK, Saini S, Bhatnagar S, Gupta N, Sapra S, et al. Prevalence of celiac disease in Indian children with Down syndrome and its clinical and laboratory predictors. Indian J Pediatr. 2013;80:114-7.
7. 7. Costa Gomes R, Cerqueira Maia J, Fernando Arrais R, André Nunes Jatobá C, Auxiliadora Carvalho Rocha M, Edinilma Felinto Brito M, et al. The celiac iceberg: from the clinical spectrum to serology and histopathology in children and adolescents with type 1 diabetes mellitus and Down syndrome. Scand J Gastroenterol. 2016;51:178-85.
8. 8. Lobe MCS, Perini LD, de Noronha MGO, Krueger MB, Castellen NR. Prevalence of autoimmune diseases in patients with Down syndrome. AMRIGS. 2013;57:5-8.

9. 9. Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102:330-54.
10. 10. Dalgic B, Sari S, Basturk B, Ensari A, Egritas O, Bukulmez A, et al. Prevalence of celiac disease in healthy Turkish school children. Am J Gastroenterol. 2011;106:1512-7.
11. 11. Kansu A, Kuloğlu Z, Demir A, Yaman A. Yield of coeliac screening in abdominal pain-associated functional gastrointestinal system disorders. J Paediatr Child Health. 2015;51:1066-70.
12. 12. Mårild K, Stephansson O, Grahnquist L, Cnattingius S, Söderman G, Ludvigsson JF. Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study. J Pediatr. 2013;163:237-42.
13. 13. Nisihara RM, Kotze LM, Utiyama SR, Oliveira NP, Fiedler PT, Messias-Reason IT. Celiac disease in children and adolescents with Down syndrome. J Pediatr (Rio J). 2005;81:373-6.
14. 14. Roizen NJ, Magyar CI, Kuschner ES, Sulkes SB, Druschel C, van Wijngaarden E, et al. A community cross-sectional survey of medical problems in 440 children with Down syndrome in New York State. J Pediatr. 2014;164:871-5.
15. 15. Alanay Y, Boduroğlu K, Tunçbilek E. Celiac disease screening in 100 Turkish children with Down syndrome. Turk J Pediatr. 2005;47:138-40.
16. 16. Pavlovic M, Radlovic N, Lekovic Z, Stojsic Z, Puleva K, Berenji K. When to screen children with Down syndrome for celiac disease? J Trop Pediatr. 2010;56:443-5.
17. 17. Işikay S, Kocamaz H. The neurological face of celiac disease. Arq Gastroenterol. 2015;52:167-70.
18. 18. Al-Qabandi W, Buhamrah E, Al-Abdulrazzaq D, Hamadi K, Al Refaee F. Celiac disease in children: is it a problem in Kuwait? Clin Exp Gastroenterol. 2014;8:43-8.
19. 19. Størdal K, Bakken IJ, Surén P, Stene LC. Epidemiology of coeliac disease and comorbidity in Norwegian children. J Pediatr Gastroenterol Nutr. 2013;57:467-71.
20. 20. Acikbas I, Tomatir AG, Akdag B, Koksal A. Retrospective analysis of live birth prevalence of children with Down syndrome in Denizli, Turkey. Genet Mol Res. 2012;11:4640-5.
21. 21. Farahid OH, Khawaja N, Shennak MM, Batieha A, El-Khateeb M, Ajlouni K. Prevalence of coeliac disease among adult patients with autoimmune hypothyroidism in Jordan. East Mediterr Health J. 2014;20:51-5.
22. 22. Paul SP, McVeigh L, Gil-Zaragozano E, Basude D. Diagnosis and nursing management of coeliac disease in children. Nurs Child Young People. 2016;28:18-24.
23. 23. Cerqueira RM, Rocha CM, Fernandes CD, Correia MR. Celiac disease in Portuguese children and adults with Down syndrome. Eur J Gastroenterol Hepatol. 2010;22:868-71.
24. 24. Barca D, Tarta-Arsene O, Dica A, Iliescu C, Budisteanu M, Motoescu C, et al. Intellectual disability and epilepsy in down syndrome. Maedica (Buchar). 2014;9:344-50.