Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome

doi:10.1067/mpd.2000.110421

The Journal of Pediatrics

Volume 137, Issue 6, December 2000, Pages 756-761

https://doi.org/10.1067/mpd.2000.110421 Get rights and content

Abstract

Objectives: To investigate the best approach to screen for celiac disease (CD) in patients with Down syndrome (DS). Study design: One hundred thirty-seven children with DS were followed up longitudinally. CD screening was offered in 1994, 1996, and 1999 by determination of serum immunoglobulin A–anti-endomysium antibodies (AEA). The HLA-DQA1*0501/DQB1*02 allelic combination known to be strongly positively associated with CD was typed. All IgA-AEA–positive children were given the opportunity to undergo a small bowel biopsy: if villous atrophy was found, the diagnosis of CD was established. Results: CD was diagnosed in 11 (8%) children: 8 in 1994 and 3 in 1996. All of them carried the HLA-DQ alleles associated with CD. The presence of symptoms was not useful in discriminating which children could have CD. Conclusions: Screening once in a lifetime is not enough to detect CD in patients with DS. We propose a new, accurate, and cost-sparing 2-step strategy for screening, based on selection of the individuals with potential CD by HLA-DQ typing and on longitudinal serologic CD screening in this selected group. (J Pediatr 2000;137:756-61)

Section snippets

SUBJECTS AND METHODS

Inclusion criteria for the children participating in the study were: having DS, being a member of the Dutch Down Syndrome Foundation, having been born in the province of “Zuid Holland,” and having had gluten introduced into the diet. Informed consent was obtained from the parents of all 137 children who were screened for CD in 1994⁷ (mean age, 5.3 years ± 3.7 SD; range, 1-17.6; male/female ratio = 1:1). Screening was offered again in 1996 and in 1999.

Clinical assessment was performed at home to

RESULTS

In 1994, 8 of the 137 screened children were given a diagnosis of CD (Fig 1).⁷

. Results of screening for celiac disease (CD) in children with Down syndrome.

In 1996, 125 of the 129 children without CD were approached again for screening: 3 children could not be contacted, and 1 child was not invited because he had developed leukemia. The parents of 85 individuals (mean age ± SD, 7.5 ± 6.5 years; range, 2.7-19.8 years; male/female ratio = 1:1.2) gave informed consent. Five children had IgA-AEA and

DISCUSSION

Our study confirms that CD is much more frequent in persons with DS than in the general Dutch population (0.5%) and that early detection and treatment of CD in children with DS improves their clinical condition and reverses the small bowel damage. Therefore all children with DS should be screened for CD. However, which approach should be used? The determination of IgA-AEA is widely accepted to be the most specific screening test.4, 7, 8 Confirming the results from others in the general

Acknowledgements

We thank Dr J. Bouquet (Sophia Children’s Hospital, Rotterdam) for providing clinical data, Dr G. M. T. Schreuder (Leiden University Medical Center) for HLA-typing analysis, and Prof Dr J. M. Wit (Leiden University Medical Center), Prof Dr S. P. Verloove-Vanhorick (TNO-PG, Leiden), and E. A. B. de Graaf (Dutch Down Syndrome Foundation) for critically reading the manuscript.

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Among the adverse reactions caused by wheat, celiac disease (CD) is the longest studied and best-known pathology. The more recently defined non-celiac gluten sensitivity (NCGS) presents with symptoms which are often indistinguishable from CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The IgA anti-transglutaminase (tTG) test is considered highly important, as it shows high sensitivity and specificity and its levels correlate to the degree of intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with IgA anti-tTG levels above 10 × the manufacturer's cut-off. Recently, tests of anti-deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA assays, especially in the IgG class, and can replace anti-tTG tests in patients with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG assays show greater sensitivity than a single test, with very high specificity. EMA tests have great diagnostic accuracy but are not recommended by all the latest guidelines because they are observer dependent. Biopsy must still be considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to screen asymptomatic children and in cases of histology/serology disagreement. About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS, first CD and wheat allergy must be excluded; then the wheat dependence of symptoms must be verified by a gluten-free diet and subsequent gluten challenge.
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Celiac disease is a complex disorder, the development of which is controlled by a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups. The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used. When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out. Diagnostic criteria include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced.
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Amendments made in the diagnostic criteria of coeliac disease over the last half century have simplified the diagnosis. However, the aspect most relevant to the specialist in internal medicine is related to its grave consequences when the disease fails to respond to a gluten-free diet. These refractory cases may culminate in severe complications with sombre endings and malignancy. Fortunately, current technology can offer the specialist in internal medicine more facilities to diagnose the cause of the complicated cases in order to attempt to intervene in the course of disease and hopefully save these patients.
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Coeliac disease profile in Down syndrome patients
2010, SD Revista Medica Internacional sobre el Sindrome de Down
Individuals with Down syndrome (DS) are a major risk group for coeliac disease (CD). The aim of this study is to find differences in the CD profile in this group in order to take a different medical approach.
This observational, descriptive and comparative study included 81 patients aged under 15 years monitored between January 1999 and December 2008. Patients were divided into two groups, a first group including 28 children with CD and DS, and a second age— and sex-matched group of 53 children with CD and no DS. Retrospective data from medical records were analyzed.
There were no statistically significant differences in age at diagnosis, clinical presentation, symptoms at diagnosis, body measurements, serological markers and histological data. Members of the DS group were significantly likelier to have no family history of CD or an association with autoimmune thyroiditis. Breastfeeding was initiated less frequently in the DS group, and the introduction of gluten was significantly delayed. The genetic study showed a significantly high frequency of the DQ8 heterodimer in patients with SD.
The clinical profile of CD in children with DS appears to be similar to that for children without this condition. The risk heterodimer distribution in DS individuals in this series differs from published data. Some nutritional features in this population could entail new risk factors that might trigger the onset of CD.
El colectivo de personas con síndrome de Down (SD) es uno de los más importantes dentro de los grupos de riesgo de enfermedad celíaca (EC). Nuestro objetivo es encontrar diferencias en el perfil de la EC en este colectivo que permitan un manejo médico diferente.
Estudio observacional, descriptivo y comparativo que incluyó a 81 pacientes menores de 15 años controlados entre enero de 1999 y diciembre de 2008. Se establecieron dos grupos; el primero incluyó a 28 niños con EC y SD y el segundo incluyó a 53 niños con EC y sin SD, ajustados por edad y sexo. Se analizaron retrospectivamente los datos procedentes de las historias clínicas.
No se encontraron diferencias estadísticamente significativas en cuanto a la edad de diagnóstico, la presentación clínica, la sintomatología al diagnóstico, la somatometría, los marcadores serológicos o los datos histológicos. Se observaron diferencias estadísticamente significativas en el grupo SD en relación con la ausencia de antecedentes familiares de EC y en la asociación con tiroiditis autoinmune. Este grupo inició menos frecuentemente la lactancia materna y la introducción del gluten fue significativamente más tardía. El estudio genético mostró una importante frecuencia de heterodímeros DQ8 en el grupo de pacientes con SD.
El perfil clínico de la EC en el niño con SD parece similar al del niño sin esta condición. La distribución de los heterodímeros de riesgo en los individuos con SD de nuestra serie difiere de los datos publicados. Existen peculiaridades nutricionales en este colectivo que podrían determinar la presencia de nuevos factores de riesgo que precipiten la aparición de una EC.
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^☆: Supported by the Dutch Ministry of Health, Welfare and Sports, Praeventiefonds/ZON, the Leiden University Research Information Center, and Astra Zeneca, the Netherlands.

^☆☆: Reprint requests: M. Luisa Mearin, MD, PhD, Leiden University Medical Center, Department of Paediatrics, J6-S-220, PO Box 9600, 2300 RC Leiden, The Netherlands.

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Original ArticlesAccuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome☆,☆☆

Abstract

Section snippets

SUBJECTS AND METHODS

RESULTS

DISCUSSION

Acknowledgements

Lancet

Lancet

Lancet

J Pediatr

Lancet

Hum Immunol

Gastroenterology

Gastroenterology

J Pediatr

Down’s syndrome and celiac disease

J Pediatr Gastroenterol Nutr

Down syndrome and celiac disease

J Pediatr Gastroenterol Nutr

Original Articles
Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome☆,☆☆