Down Syndrome Abstract
of the Month: Jan 2001
Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome
Csizmadia CG et al.
J Pediatr 2000 Dec;137(6):756-61
Departments of Pediatrics and Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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.
My comments:
First, some immunology background:
HLA stands for Human Leukocyte Antigen. The HLA genes make proteins that help the body distinguish between "self and "nonself." Without this ability, the body wouldn't be able to fight off infections, or else immune-mediated self destruction. Three different classes of HLA molecules are made by genes on the 6th chromosome. Each class has several subclasses. Certain "alleles" (variations of a single gene) of an HLA gene have been associated with certain autoimmune diseases, such as juvenile rheumatoid arthritis, lupus and celiac disease. Celiac disease has been associated with certain alleles of the genes called DQA1 and DQB1. So the authors of this study decided to screen these children with DS for these specific alleles, the first time this has been done.
The first thing to note from this study is that of the initial group of 129 children with DS that tested negative for CD in 1994, 3 children were diagnosed as having CD two years later. So one screen is not enough. In this study, the youngest child with CD was 3 years old and had no CD at a prior screen at 1 year of age. So the time for initial screening seems best suited for the third birthday.
The authors found that of all the children that eventually tested positive for CD had the combination of alleles designated as DQA1*0501 and DQB1*02, which fits the general population of people with CD. In studying the HLA types of all the children with DS in the group, the authors found no over-representation of this combination in children with DS, which is surprising to me, since children with DS have a higher risk of having CD.
Therefore, the authors suggest that the best way to screen children with DS would be to test every child for the significant HLA allelic combinations. If the child has no HLA alleles associated with CD, no further screening is necessary. If the child has HLA alleles associated with CD, then the child should be screened with the IgA-AEA test (Anti-Endomysium Antibodies) every one to two years beginning at age 2 to 3 years. A child with the positive IgA-AEA test would then be a candidate for a small bowel biopsy.
Before adopting the authors' recommendations, we need to determine if this association between children with DS and CD and the specific HLA-DQ alleles still holds in other geographic areas of the world. However, if it does hold up, it would save approximately 70% of all children with DS from being screened unnecessarily for CD.
For more information on DS and celiac disease, see my essay on the topic.