Elevated Serum Tissue Transglutaminase Antibodies in Children With Eosinophilic Esophagitis.

OBJECTIVES: This study compared the clinical and histopathological characteristics of children with eosinophilic esophagitis (EoE) and elevated anti-transglutaminase (TTG Ab) with those with EoE and normal TTG Ab titres. METHODS: Single-center chart and blinded histopathological review of patients diagnosed with EoE for a 4-year period, who had esophageal and duodenal biopsies taken at time of endoscopy, and TTG Ab measured within 6 months of biopsy. Patients with histology-proven CD were excluded. RESULTS: Elevated TTG Ab was present in 19/34 (54%) of the study cohort, representing 23% of all patients diagnosed with EoE during the study period. Eight had titers >6× upper limit of normal (ULN) and 4 had >10× ULN. TTG Ab-positive patients were classified as having either potential CD with (n = 3, 16%) and without lymphocytic duodenosis (LD; n = 12, 63%), and no CD (n = 4, 21%) on human leukocyte antigen typing. There was an increase in duodenal eosinophils in patients with elevated TTG Ab (P = 0.01), which remained when patients with LD were excluded (P = 0.018). Of 19 patients with EoE and elevated TTG Ab, 5 responded to elimination diet involving exclusion of wheat, including 2 with a sole wheat trigger and TTG Ab >10× ULN that were CD-associated human leukocyte antigen-negative. CONCLUSIONS: Serum TTG Ab was elevated in almost one-quarter of our total EoE cohort, and at least 20% of these patients did not have potential CD, suggesting EoE is a heterogeneous disease with differing immune mechanisms activated in some patients. These findings also support routine esophageal biopsy during upper endoscopy in children with elevated TTG Ab.

FOXP1 mutations cause intellectual disability and a recognizable phenotype.

Mutations in FOXP1, located at 3p13, have been reported in patients with global developmental delay (GDD), intellectual disability (ID), and speech defects. Mutations in FOXP2, located at 7q31, are well known to cause developmental speech and language disorders, particularly developmental verbal dyspraxia (DVD). FOXP2 has been shown to work co-operatively with FOXP1 in mouse development. An overlap in FOXP1 and FOXP2 expression, both in the songbird and human fetal brain, has suggested that FOXP1 may also have a role in speech and language disorders. We report on a male child with a 0.19 MB intragenic deletion that is predicted to result in haploinsufficiency of FOXP1. Review of our patient and others reported in the literature reveals an emerging phenotype of GDD/ID with moderate to severe speech delay where expressive speech is most severely affected. DVD appears not to be a distinct feature in this group. Facial features include a broad forehead, downslanting palpebral fissures, a short nose with broad tip, relative or true macrocephaly, a frontal hair upsweep and prominent digit pads. Autistic traits and other behavioral problems are likely to be associated with haploinsufficiency of FOXP1. Congenital malformations may be associated.