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Celiac Disease-Related Antibodies in Italian Children With Epilepsy
Celiac Disease-Related Antibodies in Italian Children With Epilepsy Lucio Giordano, MD*, Monica Valotti, BSc†, Adonella Bosetti, BSc†, Patrizia Accorsi, MD*, Luigi Caimi, MD†, and Luisa Imberti, MD† Reports differ on the association between epilepsy and celiac disease, an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. In this study, 272 Italian children with epilepsy and 300 healthy children were screened for antigliadin and anti-transglutaminase immunoglobulin A and G; positive and borderline samples were tested for the presence of anti-endomysium antibodies. The prevalence of antibodies related to celiac disease was comparable to that of healthy controls. In keeping with this observation, Italian epileptic children should not be considered a group at risk for celiac disease. Ó 2009 by Elsevier Inc. All rights reserved. Giordano L, Valotti M, Bosetti A, Accorsi P, Caimi L, Imberti L. Celiac disease-related antibodies in italian children with epilepsy. Pediatr Neurol 2009;41:34-36.
Introduction Celiac disease has been associated with numerous immune-mediated diseases and principally with neurologic disorders such as cerebellar ataxia, peripheral neuropathy, dementia, myelopathy, and epilepsy. Epilepsy is one of the neurologic manifestations most commonly associated with celiac disease [1], and the observed frequency ranges from 3.5% [2] to 5.5% [1] of patients with celiac disease. Conversely, in adult patients with epilepsy, the prevalence of celiac disease ranges from 1.2% to 2.5% [2], whereas in the general population of Europe and the United States it ranges from 0.27% and 0.9% [3,4]. In children, this association between epilepsy and celiac disease has been observed in epilepsies with bilateral occipital calcifications [5], in idiopathic childhood partial epilepsy with occipital paroxysms [6], and in other types of idiopathic epilepsies [7]. Ranua et al. [4], however, did not find differences of From the *Pediatric Neuropsychiatric Division and the †Biotechnology Laboratory of the Diagnostics Department, City Hospital of Brescia, Brescia, Italy.
34 PEDIATRIC NEUROLOGY Vol. 41 No. 1
celiac disease-related antibody frequency between a Finnish cohort of epilepsy patients and a matched reference population. Possible explanations for these contradictory findings include age, the fact that both conditions are rather common in the general population with considerable probability of random comorbidity, the different technological approaches used for the analysis, the small number of subjects analyzed, differences in genetic background and geographic distribution, or the preselection of patients with specific types of epilepsy. In light of this varied and sometimes contradictory literature, and to add an Italian population to the available data, the frequency of celiac disease-related antibodies was examined in a cohort of 272 unselected children with epilepsy and in a matched population-based control group coming from the same geographic area of North Italy.
Materials and Methods Informed consent was obtained, in accordance with institutional review board guidelines for the protection of human subjects, from parents or legal guardians of 272 patients (153 male, 119 female; age range, 6 months-16 years) consecutively enrolled from February 2006 to December 2006 in the Regional Pediatric Epilepsy Center of the City Hospital (Spedali Civili) of Brescia, Italy. All of the patients had been born and were resident within or nearby this city area. The diagnosis of epilepsy, according to the International Classification [8], was based on epileptiform discharges, the presence at least two unprovoked seizures occurring within a 1-month interval, and was established within 3 months from the first seizure occurrence. Patients had both awake and sleep-deprived video-electroencephalography, as well as neuroradiologic investigation. They were then periodically given comprehensive clinical, neuropsychologic, and electroencephalographic examinations. To avoid the bias of a preselected population, patients with epilepsy of unknown origin were also included, together with three epilepsy patients with a known diagnosis of celiac disease referred to the center during the period of the study. Attention was given to identifying celiac diseasespecific symptoms, such as recurrent vomiting, diarrhea, failure to grow, failure to thrive, and anemia.
Communications should be addressed to: Dr. Imberti; Diagnostics Department, Biotechnology Laboratory, Spedali Civili di Brescia, pz.le Spedali Civili, 1, 25123 Brescia, Italy. E-mail: [email protected] Received November 11, 2008; accepted February 10, 2009.
Ó 2009 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2009.02.009 0887-8994/09/$—see front matter
Table 1. Prevalence of celiac disease-related antibodies in pediatric patients with epilepsy and controls
Antibody Type IgG-AGA IgA-AGA IgG-tTG IgA-tTG
Patients (n = 272) Border-line*, Positive, no. no. 16 6 2 0
58 10 5 5
Total, no. (%) 74 (27.2) 16 (5.9) 7 (2.6) 5 (1.8)
Controls (n = 300) Border-line*, Positive, no. no. 14 1 1 0
39 5 3 3
Total, no. (%)
Odds Ratio
95% Confidence Interval
53 (17.7) 6 (2.0) 4 (1.3) 3 (1.0)
1.742 3.063 1.955 1.854
1.168-2.597 1.180-7.945 0.566-6.754 0.439-7.834
P-value† 0.007 0.017 0.365 0.486
* Samples with antibody values ranging between 7 EliA U/mL (the upper limit for negative) and 10 EliA U/mL (the lower limit for positive). The EliA units are manufacturer-specific equivalents to fluorescence units in enzyme linked immunoassay (Phadia Diagnostics, Milan, Italy). † Fisher’s exact test. Abbreviations: AGA = Anti-gliadin antibodies IgA = Immunoglobulin A IgG = Immunoglobulin G NS = Not significant tTG = Tissue transglutaminase antibodies
The control group consisted of 300 children matched for age, gender, and municipality of residence; they were recruited from among those examined in the pediatric outpatient clinic for a routine health evaluation. Medical history of all control children was recorded, and neurologic status was evaluated. The antibodies studied were immunoglobulin G-class (IgG) and immunoglobulin A-class (IgA) anti-gliadin antibodies, anti-transglutaminase antibodies (whose presence correlates with the degree of villous atrophy [9]), and IgA-class anti-endomysial antibodies. All sera were tested for anti-gliadin IgA, anti-gliadin IgG, anti-transglutaminase IgA and anti-transglutaminase IgG by use of a commercial enzyme-linked immunoassay system (ImmunoCAP and Celikey IgA and IgG assays; Phadia Diagnostics, Milan, Italy). In this system, solid-phase antigen-coated monowells are used for a fully automated quantitative detection of antibodies. The measurement range (in manufacturer-specific EliA units) was from 0.1 to more than 128 EliA U/mL. According to the manufacturer’s instructions, values of $10 EliA U/mL are considered positive, values of <7 EliA U/mL are considered negative, and those in between are defined as borderline. In selected samples, anti-transglutaminase IgA and anti-transglutaminase IgG antibodies were also quantified by means of enzyme-linked immunosorbent assay with Celikey assay for anti-transglutaminase IgA and Recombi-tTG IgG for anti-transglutaminase IgG (Phadia); anti-endomysial IgA antibodies were measured in by indirect immunofluorescence on monkey esophagus sections at a 1:5, 1:10, and 1:20 serum dilutions (Phadia).
Results Of the 272 patients, 64 had idiopathic (either partial or generalized) epilepsy, 63 had cryptogenic epilepsy, and 145 had symptomatic epilepsy due to brain damage, cerebral malformation, metabolic disorder, and degenerative disease. The prevalence of celiac disease-related antibodies is summarized in Table 1. A greater total number of samples from epilepsy patients were positive for anti-gliadin IgG and anti-gliadin IgA (including true positive and borderline) than were samples from controls: anti-gliadin IgG, 74/272 (27.2%) vs 53/300 (17.7%), P = 0.007; anti-gliadin IgA, 16/272 (5.9%) vs 6/300 (2.0%), P = 0.017. By contrast, there was no
difference between patients and controls in the prevalence of anti-transglutaminase antibodies: anti-transglutaminase IgG, 7/272 (2.6%) vs 4/300 (1.3%), P > 0.05; anti-transglutaminase IgA, 5/272 (1.8%) vs 3/300 (1.0%), P > 0.05. Both positive and borderline samples were tested for the presence of celiac disease-related antibodies by enzymelinked immunosorbent assay and for the occurrence of anti-endomysial antibodies by immunofluorescence; concordant result between the diverse assays was found only in the case of positive samples. The results were not biased by the fact that detection of anti-endomysial and anti-transglutaminase antibodies is less sensitive in children younger than 2 years [10], because the study population included only a few epilepsy patients under 2 years of age. Finally, none of the patients had isolated high anti-transglutaminase IgA. Out of the 272 epilepsy patients, only 5 showed evidence of anti-transglutaminase and anti-endomysial antibodies, which are considered surely related to celiac disease, and 2 of the 5 could be defined as silent celiac disease patients, because they have never manifested any symptoms of celiac disease. In the first case of silent celiac disease, a 6-year-old boy, the diagnosis of generalized idiopathic epilepsy was made at 4 years of age and at writing the disease was well controlled with sodium valproate therapy. Findings from neuroimaging with cranial magnetic resonance imaging and computed tomography, evaluation of psychomotor development, and neurologic examination were unremarkable. The second patient has a symptomatic focal epilepsy due to fetal distress, with drug-resistant seizures. Findings from his neurologic assessment were characterized by severe neurologic impairment with mental retardation, and by focal epileptic seizures. Both magnetic resonance imaging and computed tomography revealed a diffuse cerebral atrophy. The electroencephalography pattern was
Giordano et al: Celiac Disease and Epilepsy 35
characterized by multifocal anomalies during wake and sleep. Neither patient had ever exhibited symptoms related to celiac disease.
Discussion The only significant difference between the children with epilepsy and the controls was the higher positivity for antigliadin IgG and IgA observed in the patients. However, anti-gliadin antibody measurement has completely and justifiably fallen into disuse. Based on the quantification of anti-transglutaminase antibodies, which is now preferred for clinical use because of its sensitivity (>90%), higher specificity (95%) and reproducibility with the different available diagnostic kits [8,11], there were no differences between the two study populations. Several studies have reported an increased prevalence of epilepsy in celiac disease patients [4]. Gobbi [5] and Vascotto and Fois [12] have suggested that, in epidemiologic studies, the type of celiac disease (typical or silent and latent) and the age at diagnosis of celiac disease must be considered. Celiac disease affects only a minority of the population (1%), and this may be a limitation for small epidemiologic studies. Therefore, if we consider the numbers of subjects examined and the very low proportion of celiac disease-related antibodies found, the present results may be biased by some degree of random variability. Moreover, the present data differ from those observed by Antigoni et al. [7] in a Greek cohort, in which 5% of children with epilepsy and none of the controls had celiac disease. Study design and number of subjects are very similar between the present study and that of Antigoni et al. [7]. Possible explanations for the divergent findings include either the different genetic background or geographic origin of the two populations, or, again, sample size vs statistical variability, possibly leading to type I or type II errors.
36 PEDIATRIC NEUROLOGY Vol. 41 No. 1
In conclusion, the prevalence of celiac disease-related antibodies in epileptic children is comparable to that observed in age-matched controls of the same geographic area of North Italy, and its value is consistent with that reported on a population screening study conducted in the general Italian population [13]. References [1] Chapman RW, Laidlow JM, Colin-Jones D, Eade OE, Smith CL. Increased prevalence of epilepsy in coeliac disease. Br Med J 1978;2: 250-1. [2] Cronin CC, Jackson LM, Feighery C, et al. Coeliac disease and epilepsy. QJM 1998;91:303-8. [3] Luostarinen L, Dastidar P, Collin P, et al. Association between coeliac disease, epilepsy and brain atrophy. Eur Neurol 2001;46:187-91. [4] Ranua J, Luoma K, Auvinen A, et al. Celiac disease-related antibodies in an epilepsy cohort and matched reference population. Epilepsy Behav 2005;6:388-92. [5] Gobbi G. Coeliac disease, epilepsy and cerebral calcifications. Brain Dev 2005;27:189-200. [6] Labate A, Gambardella A, Messina D, et al. Silent celiac disease in patients with childhood localization-related epilepsies. Epilepsia 2001; 42:1153-5. [7] Antigoni M, Xinias I, Theodouli P, et al. Increased prevalence of silent celiac disease among Greek epileptic children. Pediatr Neurol 2007; 36:165-9. [8] ILAE Commission on Classification and Terminology. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99. [9] Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801. [10] Book LS. Diagnosing celiac disease in 2002: who, why, and how? Pediatrics 2002;109:952-4. [11] Ferna´ndez E, Riestra S, Rodrigo L, et al. Comparison of six human anti-transglutaminase ELISA-tests in the diagnosis of celiac disease in the Saharawi population. World J Gastroenterol 2005;11:3762-6. [12] Vascotto M, Fois A. Epilepsy and coeliac disease: a collaborative study. In: Gobbi G, Andermann F, Naccarato S, Banchini G, editors. Epilepsy and other neurological disorders in coeliac disease. London: John Libbey, 1997:105-10. [13] Volta U, Bellentani S, Bianchi FB, et al. High prevalence of celiac disease in Italian general population. Dig Dis Sci 2001;46:1500-5.
Introduction Celiac disease has been associated with numerous immune-mediated diseases and principally with neurologic disorders such as cerebellar ataxia, peripheral neuropathy, dementia, myelopathy, and epilepsy. Epilepsy is one of the neurologic manifestations most commonly associated with celiac disease [1], and the observed frequency ranges from 3.5% [2] to 5.5% [1] of patients with celiac disease. Conversely, in adult patients with epilepsy, the prevalence of celiac disease ranges from 1.2% to 2.5% [2], whereas in the general population of Europe and the United States it ranges from 0.27% and 0.9% [3,4]. In children, this association between epilepsy and celiac disease has been observed in epilepsies with bilateral occipital calcifications [5], in idiopathic childhood partial epilepsy with occipital paroxysms [6], and in other types of idiopathic epilepsies [7]. Ranua et al. [4], however, did not find differences of From the *Pediatric Neuropsychiatric Division and the †Biotechnology Laboratory of the Diagnostics Department, City Hospital of Brescia, Brescia, Italy.
34 PEDIATRIC NEUROLOGY Vol. 41 No. 1
celiac disease-related antibody frequency between a Finnish cohort of epilepsy patients and a matched reference population. Possible explanations for these contradictory findings include age, the fact that both conditions are rather common in the general population with considerable probability of random comorbidity, the different technological approaches used for the analysis, the small number of subjects analyzed, differences in genetic background and geographic distribution, or the preselection of patients with specific types of epilepsy. In light of this varied and sometimes contradictory literature, and to add an Italian population to the available data, the frequency of celiac disease-related antibodies was examined in a cohort of 272 unselected children with epilepsy and in a matched population-based control group coming from the same geographic area of North Italy.
Materials and Methods Informed consent was obtained, in accordance with institutional review board guidelines for the protection of human subjects, from parents or legal guardians of 272 patients (153 male, 119 female; age range, 6 months-16 years) consecutively enrolled from February 2006 to December 2006 in the Regional Pediatric Epilepsy Center of the City Hospital (Spedali Civili) of Brescia, Italy. All of the patients had been born and were resident within or nearby this city area. The diagnosis of epilepsy, according to the International Classification [8], was based on epileptiform discharges, the presence at least two unprovoked seizures occurring within a 1-month interval, and was established within 3 months from the first seizure occurrence. Patients had both awake and sleep-deprived video-electroencephalography, as well as neuroradiologic investigation. They were then periodically given comprehensive clinical, neuropsychologic, and electroencephalographic examinations. To avoid the bias of a preselected population, patients with epilepsy of unknown origin were also included, together with three epilepsy patients with a known diagnosis of celiac disease referred to the center during the period of the study. Attention was given to identifying celiac diseasespecific symptoms, such as recurrent vomiting, diarrhea, failure to grow, failure to thrive, and anemia.
Communications should be addressed to: Dr. Imberti; Diagnostics Department, Biotechnology Laboratory, Spedali Civili di Brescia, pz.le Spedali Civili, 1, 25123 Brescia, Italy. E-mail: [email protected] Received November 11, 2008; accepted February 10, 2009.
Ó 2009 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2009.02.009 0887-8994/09/$—see front matter
Table 1. Prevalence of celiac disease-related antibodies in pediatric patients with epilepsy and controls
Antibody Type IgG-AGA IgA-AGA IgG-tTG IgA-tTG
Patients (n = 272) Border-line*, Positive, no. no. 16 6 2 0
58 10 5 5
Total, no. (%) 74 (27.2) 16 (5.9) 7 (2.6) 5 (1.8)
Controls (n = 300) Border-line*, Positive, no. no. 14 1 1 0
39 5 3 3
Total, no. (%)
Odds Ratio
95% Confidence Interval
53 (17.7) 6 (2.0) 4 (1.3) 3 (1.0)
1.742 3.063 1.955 1.854
1.168-2.597 1.180-7.945 0.566-6.754 0.439-7.834
P-value† 0.007 0.017 0.365 0.486
* Samples with antibody values ranging between 7 EliA U/mL (the upper limit for negative) and 10 EliA U/mL (the lower limit for positive). The EliA units are manufacturer-specific equivalents to fluorescence units in enzyme linked immunoassay (Phadia Diagnostics, Milan, Italy). † Fisher’s exact test. Abbreviations: AGA = Anti-gliadin antibodies IgA = Immunoglobulin A IgG = Immunoglobulin G NS = Not significant tTG = Tissue transglutaminase antibodies
The control group consisted of 300 children matched for age, gender, and municipality of residence; they were recruited from among those examined in the pediatric outpatient clinic for a routine health evaluation. Medical history of all control children was recorded, and neurologic status was evaluated. The antibodies studied were immunoglobulin G-class (IgG) and immunoglobulin A-class (IgA) anti-gliadin antibodies, anti-transglutaminase antibodies (whose presence correlates with the degree of villous atrophy [9]), and IgA-class anti-endomysial antibodies. All sera were tested for anti-gliadin IgA, anti-gliadin IgG, anti-transglutaminase IgA and anti-transglutaminase IgG by use of a commercial enzyme-linked immunoassay system (ImmunoCAP and Celikey IgA and IgG assays; Phadia Diagnostics, Milan, Italy). In this system, solid-phase antigen-coated monowells are used for a fully automated quantitative detection of antibodies. The measurement range (in manufacturer-specific EliA units) was from 0.1 to more than 128 EliA U/mL. According to the manufacturer’s instructions, values of $10 EliA U/mL are considered positive, values of <7 EliA U/mL are considered negative, and those in between are defined as borderline. In selected samples, anti-transglutaminase IgA and anti-transglutaminase IgG antibodies were also quantified by means of enzyme-linked immunosorbent assay with Celikey assay for anti-transglutaminase IgA and Recombi-tTG IgG for anti-transglutaminase IgG (Phadia); anti-endomysial IgA antibodies were measured in by indirect immunofluorescence on monkey esophagus sections at a 1:5, 1:10, and 1:20 serum dilutions (Phadia).
Results Of the 272 patients, 64 had idiopathic (either partial or generalized) epilepsy, 63 had cryptogenic epilepsy, and 145 had symptomatic epilepsy due to brain damage, cerebral malformation, metabolic disorder, and degenerative disease. The prevalence of celiac disease-related antibodies is summarized in Table 1. A greater total number of samples from epilepsy patients were positive for anti-gliadin IgG and anti-gliadin IgA (including true positive and borderline) than were samples from controls: anti-gliadin IgG, 74/272 (27.2%) vs 53/300 (17.7%), P = 0.007; anti-gliadin IgA, 16/272 (5.9%) vs 6/300 (2.0%), P = 0.017. By contrast, there was no
difference between patients and controls in the prevalence of anti-transglutaminase antibodies: anti-transglutaminase IgG, 7/272 (2.6%) vs 4/300 (1.3%), P > 0.05; anti-transglutaminase IgA, 5/272 (1.8%) vs 3/300 (1.0%), P > 0.05. Both positive and borderline samples were tested for the presence of celiac disease-related antibodies by enzymelinked immunosorbent assay and for the occurrence of anti-endomysial antibodies by immunofluorescence; concordant result between the diverse assays was found only in the case of positive samples. The results were not biased by the fact that detection of anti-endomysial and anti-transglutaminase antibodies is less sensitive in children younger than 2 years [10], because the study population included only a few epilepsy patients under 2 years of age. Finally, none of the patients had isolated high anti-transglutaminase IgA. Out of the 272 epilepsy patients, only 5 showed evidence of anti-transglutaminase and anti-endomysial antibodies, which are considered surely related to celiac disease, and 2 of the 5 could be defined as silent celiac disease patients, because they have never manifested any symptoms of celiac disease. In the first case of silent celiac disease, a 6-year-old boy, the diagnosis of generalized idiopathic epilepsy was made at 4 years of age and at writing the disease was well controlled with sodium valproate therapy. Findings from neuroimaging with cranial magnetic resonance imaging and computed tomography, evaluation of psychomotor development, and neurologic examination were unremarkable. The second patient has a symptomatic focal epilepsy due to fetal distress, with drug-resistant seizures. Findings from his neurologic assessment were characterized by severe neurologic impairment with mental retardation, and by focal epileptic seizures. Both magnetic resonance imaging and computed tomography revealed a diffuse cerebral atrophy. The electroencephalography pattern was
Giordano et al: Celiac Disease and Epilepsy 35
characterized by multifocal anomalies during wake and sleep. Neither patient had ever exhibited symptoms related to celiac disease.
Discussion The only significant difference between the children with epilepsy and the controls was the higher positivity for antigliadin IgG and IgA observed in the patients. However, anti-gliadin antibody measurement has completely and justifiably fallen into disuse. Based on the quantification of anti-transglutaminase antibodies, which is now preferred for clinical use because of its sensitivity (>90%), higher specificity (95%) and reproducibility with the different available diagnostic kits [8,11], there were no differences between the two study populations. Several studies have reported an increased prevalence of epilepsy in celiac disease patients [4]. Gobbi [5] and Vascotto and Fois [12] have suggested that, in epidemiologic studies, the type of celiac disease (typical or silent and latent) and the age at diagnosis of celiac disease must be considered. Celiac disease affects only a minority of the population (1%), and this may be a limitation for small epidemiologic studies. Therefore, if we consider the numbers of subjects examined and the very low proportion of celiac disease-related antibodies found, the present results may be biased by some degree of random variability. Moreover, the present data differ from those observed by Antigoni et al. [7] in a Greek cohort, in which 5% of children with epilepsy and none of the controls had celiac disease. Study design and number of subjects are very similar between the present study and that of Antigoni et al. [7]. Possible explanations for the divergent findings include either the different genetic background or geographic origin of the two populations, or, again, sample size vs statistical variability, possibly leading to type I or type II errors.
36 PEDIATRIC NEUROLOGY Vol. 41 No. 1
In conclusion, the prevalence of celiac disease-related antibodies in epileptic children is comparable to that observed in age-matched controls of the same geographic area of North Italy, and its value is consistent with that reported on a population screening study conducted in the general Italian population [13]. References [1] Chapman RW, Laidlow JM, Colin-Jones D, Eade OE, Smith CL. Increased prevalence of epilepsy in coeliac disease. Br Med J 1978;2: 250-1. [2] Cronin CC, Jackson LM, Feighery C, et al. Coeliac disease and epilepsy. QJM 1998;91:303-8. [3] Luostarinen L, Dastidar P, Collin P, et al. Association between coeliac disease, epilepsy and brain atrophy. Eur Neurol 2001;46:187-91. [4] Ranua J, Luoma K, Auvinen A, et al. Celiac disease-related antibodies in an epilepsy cohort and matched reference population. Epilepsy Behav 2005;6:388-92. [5] Gobbi G. Coeliac disease, epilepsy and cerebral calcifications. Brain Dev 2005;27:189-200. [6] Labate A, Gambardella A, Messina D, et al. Silent celiac disease in patients with childhood localization-related epilepsies. Epilepsia 2001; 42:1153-5. [7] Antigoni M, Xinias I, Theodouli P, et al. Increased prevalence of silent celiac disease among Greek epileptic children. Pediatr Neurol 2007; 36:165-9. [8] ILAE Commission on Classification and Terminology. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99. [9] Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801. [10] Book LS. Diagnosing celiac disease in 2002: who, why, and how? Pediatrics 2002;109:952-4. [11] Ferna´ndez E, Riestra S, Rodrigo L, et al. Comparison of six human anti-transglutaminase ELISA-tests in the diagnosis of celiac disease in the Saharawi population. World J Gastroenterol 2005;11:3762-6. [12] Vascotto M, Fois A. Epilepsy and coeliac disease: a collaborative study. In: Gobbi G, Andermann F, Naccarato S, Banchini G, editors. Epilepsy and other neurological disorders in coeliac disease. London: John Libbey, 1997:105-10. [13] Volta U, Bellentani S, Bianchi FB, et al. High prevalence of celiac disease in Italian general population. Dig Dis Sci 2001;46:1500-5.