Elsevier

The Journal of Pediatrics

Volume 152, Issue 2, February 2008, Pages 244-249.e1
The Journal of Pediatrics

Original article
Low Prevalence of Neurologic and Psychiatric Manifestations in Children with Gluten Sensitivity

https://doi.org/10.1016/j.jpeds.2007.06.042Get rights and content

Objective

To determine the frequency of neurologic manifestations in children with gluten sensitivity (GS) and the frequency of GS in children with neurologic disease.

Study design

A total of 835 children with GS (based on positive titers for serum anti-gliadin antibody [AGA], anti-endomysial antibody [EMA], and anti-tissue transglutamine [tTG] antibody and a positive gut biopsy), representing the local childhood GS population in the town of Catania, Italy, were recruited, prospectively followed up, and screened for neurologic and psychiatric disturbances between 1991 and 2004. Serum AGA, EMA, and anti-tTG antibody titers were estimated in a prevalence sample of 630 consecutive children with neurologic disorders of unknown cause despite full investigation, 300 children with known neurologic syndromes, and 300 healthy children who served as controls. Statistical significance was assessed by the χ2 test and Yates’ χ2 test.

Results

Neurologic or psychiatric problems were noted in 15 of 835 children with GS (1.79%) with previously diagnosed GS enteropathy (GSE). In 7 of 630 children (1.1%) with a cryptogenic neurologic disorder, GS was identified based on GS autoantibody screening. These 22 children had febrile seizures, epilepsy, headache, mental retardation, neuropathy, and bipolar disorder; no children had ataxia or cerebellar disturbances. The HLAs were DQ2 (n = 16), DQ8 (n = 4), and DQ2/DQ8 (n = 2). Two of the 300 healthy controls (0.66%) had GS.

Conclusions

Based on our findings, the prevalence of neurologic/psychiatric manifestations in this group of children with GS was low but slightly higher than that in the controls (P = .041). Children with known (P = .772) and cryptogenic (P = 1.0) neurologic disorders did not exhibit a higher prevalence of GS.

Section snippets

Subject Selection

The GS clinic at the Department of Pediatrics, University of Catania is the referral center for the town of Catania (which has 336,000 inhabitants, 98,000 of whom are children) and for patients with GS or GSE and their families who live in the province of Catania in eastern Sicily (which has an overall population of 967,000 of the 5.6 million inhabitants of Sicily), as well as others from other eastern (Siracusa and Ragusa) and central (Enna and Caltanissetta) provinces of Sicily.

Between

Serologic Testing

The results of the 3 methodologically different autoantibody tests are summarized in Table I. Four of the 835 children with GS were negative on all tests and were found to have IgA deficiency. All of the 835 children with GS had positive gut biopsies. The predictive values of the antibody assays for a positive duodenal biopsy were 90.4% for AGA, 99.5% for EMA, and 99.5% for anti-tTG antibody.

Neurologic Screening in Children with GS

Of the 835 children with GS, 15 (1.79%) with previously diagnosed GSA had neurologic problems (Table II),

Discussion

In this population-based, matched-reference, prospective cohort study, we found that the childhood GS population had a very low risk (1.79%) of developing neurologic disease; however, the frequency of neurologic disease was slightly higher in the GS population than in controls (P = .041). Notably, all of the typically associated neurologic manifestations of GS occurred at low frequency, similar to that in the general population. No children with GS exhibited cerebellar dysfunction, and none of

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    Drs Ruggieri, Polizzi, and Pavone wrote the first draft of the manuscript. Drs Incorpora and Parano collaborated on recruitment and analysis of neurologic patients. Dr Spina collaborated on the diagnostic workup, follow-up, and analysis of gluten-sensitive patients. All of the authors collaborated on the second and subsequent drafts of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce this manuscript.

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