Down Syndrome & Celiac Disease

Len Leshin, M.D., F.A.A.P.

Reposted with the author's permission.
Copyright © 1997, 2000, 2002, 2004. All rights reserved

The small bowel has many roles, one of which is to absorb nutrients from our food. Celiac disease (CD) arises when the lining of the small bowel becomes damaged from exposure to gluten, the protein found in wheat, barley and rye. (Oats may be involved because oats are often contaminted with gluten from other grains during the milling process.) The small bowel becomes unable to absorb water and nutrients, causing a number of different symptoms.

Why does a child get CD? First, the disease arises only after exposure to gluten. Second, there is usually a genetic predisposition toward a "sensitive" small bowel lining. Third, certain environmental insults may make the lining more susceptible to injury from gluten, such as surgery on the gastrointestinal tract or a gastrointestinal infection. Whatever the initial reason, the gluten causes an immunologic response in the lining of the small bowel: the surface folds shrink and flatten and a "malabsorption" condition occurs. CD used to be considered to be much more common in Europe than in the US, but recent studies indicate that the incidence of CD in people in the US of European ancestry have the same incidence as in Europe. People of African-Caribbean and far Eastern Asian ancestry very rarely have CD.

Studies in the 1990s indicated that children with DS are at a higher risk to develop CD than the general population. The reasons for that aren't entirely clear, but since children with DS are at a greater risk from auto-immune diseases, that CD represents another one of these type of diseases. Studies from Europe looking at the percentage of children with DS that have CD have ranged from 7% to 16%. One American study found 4 to 5% of children with Down syndrome living on the East Coast had positive CD, but almost all the subjects were Caucasian, so this group was mostly of European heritage to begin with. Another American study done in the southeastern US found 7% of the children with DS studied had CD.

The signs of CD are varied, since the condition may be mild in some and severe in others. The majority of children with CD have what's called "failure to thrive:" lack of growth of weight, and sometimes height as well. Most have diarrhea, and/or vomiting. Children with CD are irritable and usually have a decreased appetite. The stools may be foul smelling, and in occasional cases, may not be loose but big and bulky. A small number of children will develop severe diarrhea leading to dehydration. The children who have had CD for several months will have bloating of the stomach and a loss of muscle mass. If not treated, malabsorption will continue to cause undernourishment, producing anemia, osteoporosis and peripheral neuropathy.

The main way of diagnosing CD has always been through biopsy of the small bowel. Under a microscope, the small bowel will show characteristic damage to the lining. One way this is done by having the patient swallow a capsule attached to a string, which is used to retrieve the capsule after a period of time. Many doctors prefer to do a biopsy under direct endoscopy, however, especially in children. The lining of the small bowel has certain characteristics under a microscope when CD is present.

Since a small bowel biopsy is neither easy nor cheap, it's not in the best interest of the child or family to do a biopsy on every child with DS. So the best thing would be to have an easy blood test that can detect the children who need the diagnostic biopsy. A few blood tests have been tried in the past with unhelpful results, such as the antigliadin antibody (AGA) test, which is pretty much abandoned now. The next blood test developed looks for antiendomysium (or antiendomysial) antibodies (EMA). While the EMA test is superior to the antigliadin test, the interpretation of the test is operator-dependent and prone to errors. The newest blood test looks for IgA antibodies to the enzyme transglutaminase (TG). TG is an intracellular enzyme that binds gliadin and starts to process it in a way that starts the autoimmune sequence in CD. As the TG test has turned out to be a very sensitive and specific screening test for CD, it has become the favored screening test, especially for children and adults who have no symptoms of CD. Note that all these tests are measuring IgA levels of the antibodies. One problem is that IgA deficiency may occur in people with CD, and therefore the IgA markers for CD may not show up. That would classify as a "false negative." For that reason, every time a person has blood tests for CD, the doctor should also test for total IgA levels.

Recent research has found that 97 to 98% of all cases of CD are found in people with certain genetic markers. These genetic markers are called HLA ("human leukocyte antigen") markers. There are two markers that are associated with CD: HLA-DQ2 and HLA-DQ8. In cases where CD is suspected and there is an IgA deficiency, these markers can be looked for instead to determine if a small bowel biopsy is warranted. Children with DS and CD also have the same markers. Interestingly, the genes for the HLA markers are on the chromosome 6, so the connection to chromosome 21 still needs to be discovered.

It's important to note that infection from Giardia, a microscopic parasite found worldwide, can mimic CD. Diagnosis of this infection is done by special tests on the stools.

Treatment is both simple and difficult: a gluten-free diet. All wheat, barley and rye products are off limits. Currently, it is recommended that oats be also eliminated from the diet at the beginning. They can be replaced in the diet as soon as the patient is doing better. In most cases, the symptoms of CD resolves in 2 weeks! The older the child, the longer it takes to come under control. CD is a lifelong disease; symptoms may from time to time subside to the point of the CD appearing to be gone, but the person must continue on the diet to avoid illness. The person may need vitamin supplementation to complete the diet.

For more information on the internet about celiac disease, see:

References:

Hilhorst MI et al. Down syndrome and coeliac disease: five new cases with a review of the literature. Eur J Pediatr 152: 884-887, 1993.

Jansson U & Johansson C. Down syndrome and celiac disease. J Pediatr Gastroent Nutr 21:443-445, 1995.

George EK at al. High frequency of celiac disease in Down syndrome. J Peds 128:555-557. April 1996.

Gale L et al. Down's syndrome is strongly associated with coeliac disease. Gut 40:492-496, 1997.

Carlsson A et al. Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome. Pediatrics 101(2):272-275, Feb 1998.

Pueschel SM et al. A prevalence study of celiac disease in persons with Down syndrome residing in the United States. Acta Paediatr 88:953-956, 1999.

Zachor DA et al. Prevalence of celiac disease in Down syndrome in the United States. J Pediatr Gastroenterol Nutr 31(3):275-9, 2000.

Jason SR et al. Celiac disease. Current Opin in Gastroent 17:118-126, 2001.

Carnicer J et al. Prevalence of coeliac disease in Down's syndrome. Europ J Gastroent Hepatol 13:263-267, 2001. [study of population in Spain]

Agardh D et al. Tissue transglutaminase autoantibodies and human leucocyte antigen in Down's syndrome patients with coeliac disease. Acta Paediatr 91:34-38, 2002.

Hill ID et al. Guideline for the Diagnosis and Treatment of Celiac Disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 40:1-19, Jan 2005.

Hanson T et al. Antitissue transglutaminase and antithyroid autoantibodies in children with Down syndrome and celiac disease. J Pediatr Gastroenterol Nutr. 40:170-174, Feb 2005.

Nisihara RM et al. Celiac disease in children and adolescents with Down syndrome. (Brazilian study) Jornal de Pediatria, 81:373-378, 2005.