What is the investigation with the highest diagnostic value for a patient with Down syndrome (Trisomy 21) presenting with chronic diarrhea, abdominal pain, elevated Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT), and Iron Deficiency Anemia (IDA)?

From the Guidelines

The investigation with the highest diagnostic value for a patient with Down syndrome presenting with chronic diarrhea, abdominal pain, elevated liver enzymes (AST/ALT), and iron deficiency anemia (IDA) is an upper endoscopy with duodenal biopsies to test for celiac disease. This procedure allows direct visualization of the small intestinal mucosa and collection of tissue samples to assess for the characteristic villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes seen in celiac disease. Individuals with Down syndrome have a significantly higher prevalence of celiac disease (approximately 5-10%) compared to the general population 1. The combination of gastrointestinal symptoms, elevated liver enzymes, and iron deficiency anemia strongly suggests malabsorption, with celiac disease being the most likely diagnosis in this context. While serologic testing for tissue transglutaminase antibodies and endomysial antibodies can be helpful screening tools, the duodenal biopsy remains the gold standard for diagnosis, as stated in the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1.

Some key points to consider in the diagnosis and management of celiac disease in patients with IDA include:

• Celiac disease is present in 2% to 6% of asymptomatic patients with IDA 1
• Patients with celiac disease who are anemic at presentation tend to have higher antitissue transglutaminase levels and higher degrees of villous atrophy than nonanemic patients 1
• ID occurs in celiac disease as a result of epithelial cell injury, which disrupts normal absorption 1
• In most patients without another explanation for ID, anemia will improve after initiation of a strict gluten-free diet even without iron supplementation 1

Early diagnosis and implementation of a strict gluten-free diet can resolve symptoms, normalize liver enzymes, correct nutritional deficiencies, and prevent long-term complications associated with untreated celiac disease. According to the AGA clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anemia, testing for celiac disease is an essential part of the diagnostic workup for patients with IDA, especially those with gastrointestinal symptoms and elevated liver enzymes 1.

From the Research

Diagnostic Approach

To determine the investigation with the highest diagnostic value for a patient with Down syndrome presenting with chronic diarrhea, abdominal pain, high AST/ALT, and iron deficiency anemia (IDA), we need to consider the potential underlying causes of these symptoms.

• The combination of IDA, chronic diarrhea, and abdominal pain in a patient with Down syndrome suggests the possibility of celiac disease, which is known to be more prevalent in individuals with Down syndrome 2, 3.
• Celiac disease can cause villous atrophy in the small intestine, leading to malabsorption of nutrients, including iron, and can present with a range of gastrointestinal and extraintestinal symptoms 3, 4.
• The diagnostic gold standard for celiac disease is the histological examination of duodenal biopsies, which can show villous atrophy and other characteristic changes 3, 5, 6.
• Recent studies have highlighted the importance of duodenal bulb biopsy in increasing the diagnostic yield of celiac disease, as it can detect more cases compared to biopsies taken from the distal duodenum alone 5.
• Serological tests, such as tissue transglutaminase antibodies, can also be useful in the diagnostic work-up of celiac disease but may not be as sensitive or specific as duodenal biopsy 2, 3.

Investigation with Highest Diagnostic Value

Based on the evidence, the investigation with the highest diagnostic value for this patient would be:

• Duodenal biopsy, specifically including biopsy of the duodenal bulb, as it provides a direct assessment of the small intestinal mucosa and can detect villous atrophy and other changes characteristic of celiac disease 5, 6.
• This should be complemented by serological testing, such as tissue transglutaminase antibodies, to support the diagnosis and monitor response to treatment 2, 3.