What is the most appropriate next step for an 18-month-old child with a family history of celiac disease, normal growth and weight, and no symptoms, whose older sibling has celiac disease?

Order tissue transglutaminase IgA (tTG-IgA) test

The most appropriate next step is to order serologic screening with IgA tissue transglutaminase (tTG-IgA) antibodies along with total serum IgA levels, as first-degree relatives of patients with celiac disease have a 10-15% lifetime risk and warrant screening even when asymptomatic. 1, 2

Why Screening Is Indicated

• First-degree relatives represent a high-risk population that specifically requires serologic screening according to the American Gastroenterological Association, regardless of symptom status 1, 2
• The 10-15% lifetime risk in first-degree relatives is substantially higher than the 0.5-2% prevalence in the general population, making this child's risk approximately 10-fold elevated 1, 3
• Early detection allows intervention before symptoms, complications, or nutritional deficiencies develop, including malabsorption and associated autoimmune conditions 1

Recommended Testing Strategy

• Initial screening should include tTG-IgA combined with total IgA measurement, which has 90-96% sensitivity and >95% specificity 1, 2, 4
• Total IgA levels must be verified because selective IgA deficiency occurs in 1-3% of celiac disease patients and would cause false-negative tTG-IgA results 1
• If IgA deficiency is detected, switch to IgG-based tests (IgG tTG or IgG EMA) 1, 2

Critical Pre-Testing Requirement

• The child must remain on a gluten-containing diet until testing is complete to avoid false-negative results 1, 2
• Never start a gluten-free diet before completing diagnostic workup, as this leads to false-negative serology and inconclusive biopsies 1

Why Reassurance Alone Is Inadequate

• Current guidelines do not support simply reassuring parents without screening when a first-degree relative has celiac disease 1, 2
• The absence of symptoms does not eliminate risk—many children with celiac disease are asymptomatic or have subtle presentations like constipation rather than classic diarrhea 5, 4
• Normal growth and weight do not exclude celiac disease, as extra-intestinal manifestations (iron deficiency anemia, delayed puberty, dental enamel defects) may be the only findings 6, 7, 4

Why Starting a Gluten-Free Diet Is Inappropriate

• A gluten-free diet should never be initiated without diagnostic confirmation, as it represents a significant lifelong dietary burden requiring strict adherence 1, 7
• Starting the diet prematurely makes future diagnostic testing unreliable and would require a prolonged gluten challenge (at least three slices of wheat bread daily for 1-3 months) to re-establish diagnosis 1
• Biopsy confirmation is recommended, especially in asymptomatic children, before prescribing significant dietary changes 8, 1

Parent Education Points

• Educate parents about symptoms warranting immediate attention: poor weight gain or growth failure, unexplained irritability or behavioral changes, gastrointestinal symptoms, or iron deficiency anemia 1, 4
• If the child develops type 1 diabetes in the future, immediate screening with tTG-IgA would be indicated per American Diabetes Association guidelines 8
• Screening should be repeated within 2 years of initial testing and again after 5 years, or more frequently if symptoms develop 8

Follow-Up Based on Results

• If tTG-IgA is positive: Proceed to upper endoscopy with duodenal biopsy (at least 6 specimens from the second part of the duodenum or beyond) for histological confirmation 1, 4
• If tTG-IgA is negative: Reassure parents but maintain vigilance for symptom development and repeat screening as recommended 8