Celiac Disease & Down Syndrome Abstracts

Pediatr Int 45 (4): 395-9 (2003 Aug)

Celiac disease in children with Down syndrome: Importance of follow-up and serologic screening

Cogulu O, Ozkinay F, Gunduz C, Cankaya T, Aydogdu S, Ozgenc F, Kutukculer N, Ozkinay C
Departments of Pediatrics and Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey

Background: Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is important in the diagnosis and screening for celiac disease. Antiendomysial antibodies have greater sensitivity compared to antigliadin antibodies. It has been reported that the prevalence of celiac disease is higher in children with Down syndrome than the other autoimmune conditions. The aim of the present study was to investigate the incidence of celiac disease in children with Down syndrome, to assess the availability of Ig-A AGA and EMA for serologic screening, and to highlight the importance of follow-up for children with Down syndrome. Methods: Forty-seven children with Down syndrome without known celiac disease were tested for total blood count, thyroid function tests, immunoglobulin values, Ig-A AGA and EMA. Duodenal biopsy was performed on eight patients who showed at least one serologically positive marker. Results: The ages of the children with Down syndrome ranged from 2 to 18 years (30 boys/17 girls). The mean age was 6.55 ± 3.88. Total blood count and immunoglobulin values were normal. Eleven of the 47 patients (23.40%) were found to be serologically positive, 10 (21.28%) having antigliadin antibody concentrations above normal; and six (12.77%) being positive for antiendomysial antibody. In five patients (10.64%), both Ig-A AGA and EMA concentrations were high and positive. Duodenal biopsies of three of eight cases (37.50%) revealed villous atrophy, lymphocyte infiltration and crypt hyperplasia. Three cases with abnormal biopsy results (100%) were below the 10th percentile for weight and height. Hypo-thyroidism was detected in one of 11 cases where at least one serologic marker was positive. Conclusion: Children with Down syndrome should be carefully examined in their follow up, and celiac disease should be considered in cases with growth retardation. Ig-A antigliadin antibodies and EMA are non-invasive, cheap and readily available serologic screening tests for celiac disease, and the positivity of both markers gives the most reliable result.
Dig Liver Dis 34 (2): 116-21 (2002 Feb)

Evaluation of coeliac disease serological markers in Down syndrome patients

Rumbo M; Chirdo FG; Ben R; Saldungaray I; Villalobos R
Catedra de Immunologia, Facultad de Ciencias Exactas, UNLP, La Plata, Argentina

BACKGROUND: The increased incidence of coeliac disease in patients with Down syndrome makes screening of coeliac disease in this population advisable. AIM: Evaluation of efficiency of different serological markers to detect coeliac disease in Down syndrome patients. PATIENTS: A total of 56 Down syndrome patients (aged: 1-17 years) were included in study. METHODS: Patients were evaluated for both IgG and IgA anti-transglutaminase antibodies and for anti-gliadin IgA and IgG antibodies using either purified omega-gliadin, wheat ethanol extract or commercial gliadin. Patients who had at least one positive result were evaluated for antiendomysium antibodies using either monkey oesophagus or human umbilical cord by indirect immunofluorescence. Coeliac disease was diagnosed by typical histological changes on duodenal mucosa. RESULTS: Increased levels of at least one anti-gliadin IgA and IgG antibody marker were found in 27 out of 56 cases (26 for IgG and 9 for IgA). 11/56 were positive for IgG anti-transglutaminase antibodies and two of them were also positive for IgA anti-transglutaminase antibodies and anti-endomysium antibodies. These two patients were finally diagnosed as coeliacs. Gliadin antigenic fractions employed produced differences in the performance of the anti-gliadin IgA and IgG antibody test. The use of commercial gliadin or wheat ethanol extract showed low sensitivity in IgA anti-gliadin IgA and IgG antibody determination, whereas good sensitivity and specificity were observed with omega-gliadins. IgG anti-transglutaminase antibodies showed a high proportion of false positive results (9 out of 56), whereas anti-endomysium antibodies and IgA anti-transglutaminase antibodies presented an excellent correlation with presence of active coeliac disease. CONCLUSIONS: Two out of 56 Down syndrome patients were diagnosed as coeliacs, corresponding to an incidence of 3.6%. The use of omega-gliadin presented the best efficiency in anti-gliadin IgA and IgG antibody determination whereas IgA anti-transglutaminase antibodies and anti-endomysium antibody determination showed an absolute correlation with presence of active coeliac disease.
Acta Paediatr 88 (9): 953-6 (1999 Sep)

A prevalence study of celiac disease in persons with Down syndrome residing in the United States of America

Pueschel SM, Romano C, Failla P, Barone C, Pettinato R, Castellano Chiodo A, Plumari DL
Child Development Center, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA

In order to estimate the prevalence of celiac disease in persons with Down syndrome, 105 patients with this chromosomal disorder residing on the East Coast of the United States of America were enrolled in this study. IgA and IgG antigliadin antibodies (AGA) were determined using a fluorescent immunoenzymatic assay, and antiendomysium antibodies (AEA) were measured with immunofluorescence on monkey oesophagus. Of the 105 patients, 5 were positive for AEA, 4 were positive for IgG AGA, and 1 was positive for IgG AGA and AEA. Of the five patients with high titres of AEA, four consented to a jejunal biopsy, which revealed significant villous atrophy. Thus, 4 (possibly 5) patients in this cohort of 105 individuals with Down syndrome have celiac disease.
Pediatrics 101 (2): 272-5 (1998 Feb)

Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome

Carlsson A; Axelsson I; Borulf S; Bredberg A; Forslund M; Lindberg B; Sjoberg K; Ivarsson SA
Department of Pediatrics, University of Lund, University Hospital, Malmo, Sweden

OBJECTIVE: This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome. MATERIAL AND METHODS: Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy. RESULTS: None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy. CONCLUSIONS: EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome.
Gut 40 (4): 492-6 (1997 Apr)

Down's syndrome is strongly associated with coeliac disease

Gale L; Wimalaratna H; Brotodiharjo A; Duggan JM
Hunter Region Developmental Disability Service, Stockton Centre, NSW, Australia

We screened 115 children with Down syndrome for celiac disease, using antigliadin, antiendomysium, and antireticulin serum antibodies and an intestinal permeability test. Celiac disease was diagnosed in eight children, giving a frequency of 7.0%. We recommend screening for celiac disease in all persons with Down syndrome, with the use of at least the antiendomysium antibody determination.
Acta Paediatr 85 (12): 1503-5 (1996 Dec)

Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies

Bonamico M; Rasore-Quartino A; Mariani P; Scartezzini P; Cerruti P; Tozzi MC; Cingolani M; Gemme G
I Clinica Pediatrica Università La Sapienza, Roma, Italy

The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61 children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in 6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD (3.5%). In three AGA-positive and EMA-positive subjects, permission for intestinal biopsy was refused, while in two AGA-positive and EMA-negative children, the intestinal mucosa was normal. Our study confirms the association of CD and DS, and suggests the usefulness of EMA determination as a test for selecting DS patients for intestinal biopsy.
J Pediatr Gastroenterol Nutr 23 (3): 303-306 (1996 Oct)

Celiac disease in Down's syndrome with HLA serological and molecular studies

Failla P, Ruberto C, Pagano MC, Lombardo M, Bottaro G, Perichon B, Krishnamoorthy R, Romano C, Ragusa A

The association between Down's syndrome (DS) and celiac disease (CD) has been confirmed by several authors. The sensitivity and specificity of antigliadin antibodies (AGAs), the clinical features of subjects with DS and CD (DS-CD+), the incidence of CD, and the results of serological and molecular class I and II HLA typing were determined in a sample of 57 Sicilian subjects with DS. Six (10.5%) and 17 subjects (29.8%) showed high levels of IgA AGAs and IgG AGAs, respectively. AGAs sensitivity and specificity were lower than in the population without DS. Ten people with DS were submitted to jejunal biopsy, and seven (12.2%) showed CD according to ESPGAN criteria. All seven patients were put on gluten-free diet, followed by rapid disappearance of symptoms. Class I and II HLA serological and molecular typing was carried out in seven DS-CD + subjects, 22 people with DS without CD (DS-CD-), five subjects with CD without DS, and 20 controls. Between DS-CD + and DS-CD- subjects, no statistically significant difference regarding serum HLA class I antigens was found. DQA1*0101 allele appears significantly in DS-CD + patients and deserves to be searched for in a larger sample to assess its meaning in the DS-CD association.
J Pediatr 128 (4): 555-7 (1996 Apr)

High frequency of celiac disease in Down syndrome

George EK, Mearin ML, Bouquet J, von Blomberg BM, Stapel SO, van Elburg RM, de Graaf EA

BACKGROUND: There is evidence of an increased prevalence of coeliac disease in Down's syndrome. AIMS: To investigate the association, patients with Down's syndrome and matched controls were examined. METHODS: Fifty nine patients with Down's syndrome residing in government institutions in the Hunter region of New South Wales were studied. Four were excluded (terminally ill = 1, uncooperative = 3). Each of 55 patients was matched for age, sex, and residence with a control patient. Patients with both positive IgA and IgG antigliadin antibodies were considered for endoscopical duodenal biopsy. RESULTS: Twenty one patients and two controls had raised IgA and IgG antibodies (chi 2 = 19.4; p < 0.001). Tissue was obtained in 18 patients. Two had characteristic flat, five pronounced lymphocytic infiltration not diagnostic of coeliac disease, two giardiasis, and eight were normal. In one the tissue was not suitable for analysis. There were few differences between the subgroups in their anthropomorphic, biochemical, or haematological findings. CONCLUSIONS: The prevalence of coeliac disease in these 51 patients with Down's syndrome is at least two (3.9%; 95% confidence interval (95% CI) 0%-9.2%) and could be as many as seven (13.7%; 95% CI 4.3%-23.2%). In this community the prevalence of coeliac disease in Down's syndrome is increased more than 100-fold (x135-473).
J Pediatr Gastroenterol 21 (4): 443-445 (1995 Nov 1)

Down syndrome and celiac disease

Jansson U, Johansson C

Down syndrome is associated with immune-related disorders such as hypothyroidism, insulin-dependent diabetes mellitus, and celiac disease. In this study we determined antigliadin antibodies (AGA) in 54 patients with Down syndrome; 22 had AGA values above the cutoff limit. Nineteen patients underwent intestinal biopsy, and total or subtotal villous atrophy was found in nine. There was a total of 65 patients with Down syndrome in our area of southern Sweden; two were already known to have celiac disease. The minimum prevalence of celiac disease in Down syndrome in this area in southern Sweden was 11 of 65 or 16.9%.
Pediatr Med Chir 16 (5): 467-470 (1994 Sep)

Celiac disease in children with Down's syndrome

Lazzari R, Collina A, Arena G, Corvaglia L, Marzatico M, Vallini M, Bochicchio A, Pasetti A, Frassineti S, Forchielli L

The coexistence of Down's syndrome (DS) and coeliac disease (CD) has been occasionally reported and both diseases are often related to autoimmune disorders. The pathogenetic factor that links CD and DS may be an altered immune system and/or the presence of a common genetic factor. Some epidemiological investigations, performed in patients with CD, showed an increased incidence of DS compared to the natural incidence of this abnormality in the general population. We studied the prevalence of CD in 83 individuals with DS compared to a group of 200 patients with other gastroenterologic disorders and a random scholastic sample of 500 non symptomatic children. IgG and IgA antigliadin antibodies (AGA) were determined in all patients. Antiendomysium antibodies (EmA) were investigated in all the patients of the first group, while in the other two groups, 27 and 108 cases respectively, selected by AGA positivity, were investigated for EmA. The percentage of AGA IgA positivity in the first group was 31.3% (26/83), in gastroenterologic controls 10% (20/200), in scholastic sample 2.8% (14/500), that shows a significant statistical difference. On the contrary EmA were positive in quite a similar percentage in the three groups. Duodenal [correction of Jejunal] biopsies, were performed in 11 DS patients and in 9 of the other two groups. EmA were positive only in the case with subtotal atrophy in all the groups: 5/11 in the first, 2/4 in the second, 2/5 in the third. On the contrary AGA IgA were often positive also in patients with non coeliac histologic findings.
Eur J Pediatr 152 (11): 884-887 (1993 Nov)

Down syndrome and coeliac disease: five new cases with a review of the literature

Hilhorst MI, Brink M, Wauters EA, Houwen RH
Department of Gastro-Enterology, Wilhelmina Children's Hospital, Utrecht, The Netherlands

We report five new patients with coeliac disease and Down syndrome and review the 11 cases previously reported in the literature. In 14 of these 16 patients diarrhoea was the presenting symptom and in 2 failure to thrive in combination with anaemia. The frequency of coeliac disease in children with Down syndrome was calculated as being 43 times greater than in children without Down syndrome. Delay between first symptoms and diagnosis in patients with combined coeliac disease and Down syndrome was 2.5 years, while in the other children with coeliac disease it was only 8 months. This distinctive difference could be caused by an underestimation of the seriousness of gastro-intestinal complaints in patients with Down syndrome. It is stressed that coeliac disease should be strongly considered in all children with Down syndrome and either persistent diarrhoea or failure to thrive.
American Journal on Mental Retardation 95 (1): 120-122 (1990 Jul)

Coexistence of Celiac Disease and Down Syndrome

Simila, Seppo; Kokkonen, Jourma

Three Finnish patients with Down syndrome and celiac disease are described. The incidence of celiac disease among patients with Down syndrome was calculated to be 20 times greater than in children without Down syndrome, indicating that it should be kept in mind when patients suffer from recurrent diarrhea and/or delayed puberty.
J Pediatr Gastroenterol Nutr 10 (1): 41-43 (1990 Jan)

Down's syndrome and coeliac disease

Dias JA, Walker-Smith J

The association of congenital abnormalities and gastrointestinal tract diseases has been described. The coincidence of Down's syndrome and coeliac disease has been occasionally reported, but a clear relation is not definitely established. Reviewing 190 patients with coeliac disease diagnosed at Queen Elizabeth Hospital, London, from 1960 to 1985 an increased incidence of Down's syndrome compared to the natural incidence of this abnormality in the general population was found. The age of the mothers was well below that where a reverse in the incidence of Down's syndrome is expected, and it appears therefore that this anomaly and coeliac disease may be linked. This possibility should be bourne in mind when evaluating children with Down's syndrome and gastrointestinal symptoms.