Is anti-tissue transglutaminase (a-tTG) Immunoglobulin A (IgA) indicated in cases of short stature?

Anti-Tissue Transglutaminase IgA Testing in Short Stature

Anti-tissue transglutaminase IgA (a-tTG IgA) testing is indicated in the evaluation of children with short stature, especially when no other cause has been identified. 1, 2

Rationale for Testing

• The prevalence of biopsy-confirmed celiac disease is approximately:

  • 7.4% in all-cause short stature 1
  • 11.6% in idiopathic short stature (where no other cause has been found) 1

• The American Gastroenterological Association specifically recommends that testing for celiac disease should be selectively considered in children with short stature, particularly if symptoms compatible with celiac disease are present 2

Diagnostic Approach

First-line Testing

• IgA tissue transglutaminase (tTG-IgA) is the preferred initial test for celiac disease screening 2, 3
• Total serum IgA should be measured simultaneously to rule out IgA deficiency 3

In Case of IgA Deficiency

• If IgA deficiency is present, IgG-based testing should be performed:
  • IgG deamidated gliadin peptide (IgG-DGP) antibodies
  • IgG tissue transglutaminase (IgG-tTG) 2, 3

Clinical Indicators That Strengthen the Case for Testing

Several factors increase the likelihood of celiac disease in short stature patients:

• Chronic diarrhea (OR 15.7) 4
• Anemia (OR 4.9) 4
• Height more than 3 SD below mean for age and sex 5
• Delayed bone age 6
• Family history of celiac disease 6

Testing Performance

• IgA tTG has excellent sensitivity (90-96%) and specificity (>95%) 2, 3
• Multiple studies have demonstrated that celiac disease testing in short stature patients yields significant positive results:
  • In one study, 11% of patients with short stature had celiac disease 4
  • Another study found celiac disease in 59.1% of selected short stature patients 6

Important Considerations

1. Testing must be performed while the patient is on a gluten-containing diet 2
2. Positive serologic results should be confirmed with duodenal biopsies 2
3. If clinical suspicion remains high despite negative serology, intestinal biopsy should still be pursued 2
4. Response to a gluten-free diet can improve growth velocity (mean 8.1 cm/year in one study) 4

Pitfalls to Avoid

• Relying solely on IgG antibodies as first-line testing (unless IgA deficiency is present)
• Testing after gluten restriction has begun (may lead to false negatives)
• Failing to consider celiac disease in short stature without gastrointestinal symptoms
• Using older gliadin antibody tests, which have lower sensitivity and specificity than modern tTG testing 3

In conclusion, a-tTG IgA testing should be included in the diagnostic evaluation of children with short stature, particularly when no other cause has been identified, as approximately 1 in 9 children with idiopathic short stature may have celiac disease.