Screening of coeliac disease in north Italian children with type 1 diabetes: limited usefulness of HLA-DQ typing

Aim: To determine the contribution of HLA-DQA1* and HLA-DQB1* genes to the risk of coeliac disease (CD) in a cohort of children with type 1 diabetes mellitus (T1DM) from northern Italy. Methods: Three hundred and fifty-seven children with T1DM, attending the Childhood Diabetes Unit of the University of Verona, have been regularly tested for serum IgA endomysial antibodies (EMA). All patients with positive EMA underwent small bowel biopsy to confirm the diagnosis of CD. HLA typing was performed in subjects with T1DM and CD, and in a control group of 79 EMA-negative patients with T1DM. Results: Of the 357 patients tested, 25 (7%) had CD. The frequency of HLA- DQA1*0501-DQB1*0201 (T1DM + CD 68% vs T1DM 62%) and of DQA1*0301-DQB1*0302 (T1DM + CD 40% vs T1DM 35%) haplotypes, between T1DM patients with and without CD, was statistically comparable. A trend towards a reduction of the risk of CD (p = 0.055, OR: 0.22, CI 0.05: 1.04) was observed in patients with T1DM (28% vs T1DM + CD 2%) who did not carry either the HLA-DQA1*0501-DQB1*0201 or the DQA1*0301-DQB1*0302 haplotype.

Conclusion: A high prevalence of HLA-DQA1* and -DQB1* susceptibility haplotypes for CD was observed both in EMA-negative diabetics and in those with associated CD. The implementation of screening programmes of CD in a T1DM population, based on the identification of HLA susceptibility haplotypes, seems to be of limited usefulness. Serial serologic screening of diabetic patients remains the advisable strategy.     

Coeliac disease and Cornelia de Lange syndrome: lack of association

OBJECTIVES: Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by growth and mental retardation, abnormalities of the upper limbs, gastroesophageal dysfunction, cardiac, ophthalmologic and genitourinary anomalies, hirsutism and characteristic facial features. Growth retardation, behavioural disturbances and gastro-intestinal manifestations can mimic coeliac disease (CD). Genetic conditions like Down, Williams and Turner syndromes can be associated to CD. AIM: To establish if gastro-intestinal signs and symptoms in CdLS patients are due to CD. METHODS: Multiple duodenal biopsies were performed in 24 CdLS patients (mean age 12 years) during the endoscopic follow-up for gastro-esophageal reflux disease (GERD). Histological assessment was performed. Anthropometric parameters were recorded and plotted on the growth charts specific for CdLS patients. Antiendomysium and antitransglutaminase antibodies and HLA-DQ2/DQ8 were tested in all patients. RESULTS: All CdLS patients were growth retarded, although weight and height were within the normal limits using the specific growth charts for CdLS. No histological abnormalities were noted in the intestinal biopsy specimens. Serum levels of antiendomysium and antitransglutaminase antibodies were always normal. The HLA-DQ2/DQ8 was absent in all patients. CONCLUSIONS: While a high prevalence of gastro-intestinal disorders has been described in CdLS children, no association with CdLS has been found.     

Patchy villous atrophy of the duodenum in childhood celiac disease

OBJECTIVES: Patchy villous atrophy of the duodenal mucosa has been described in adults with untreated celiac disease (CD) but not in children. The authors evaluated the presence and the distribution of villous atrophy in children with celiac disease to see whether this histologic pattern exists in children. METHODS: We studied 95 children at diagnosis (Group 1) and seven during gluten challenge (Group 2). We measured anti-endomysium antibodies (EMA) by immunofluorescence on monkey esophagus, antihuman-tissue transglutaminase autoantibodies (anti-tTG Abs) by radioimmunoprecipitation, and HLA-DQ2/DQ8 heterodimers by polymerase chain reaction using specific primers. During upper intestinal endoscopy, at least five duodenal biopsy samples were obtained, one from the duodenal bulb and four from the distal duodenum. RESULTS: Thirteen of 95 (13.7%) patients in Group 1 and in 3 of 7 (42.9%) in Group 2 had patchy villous atrophy of the duodenum. In all 16 patients, villous atrophy of the bulb was present. In four children from Group 1, villous atrophy was observed only in the bulb samples. EMA, anti-tTG Abs, and HLA-DQ2/DQ8 heterodimers were present in all patients. Fourteen of 16 had symptomatic CD, and two were silent, detected during screening in subjects at risk for CD. CONCLUSIONS: This is the first study demonstrating that children with CD may have patchy villous atrophy of the duodenum. The bulb mucosa may be the only duodenal area involved, both at diagnosis and after gluten challenge. Therefore, multiple endoscopic biopsies should always be performed, not only in the distal duodenum, but also in the bulb.     

Tissue transglutaminase autoantibodies and human leucocyte antigen in Down's syndrome patients with coeliac disease

The association between autoantibodies against tissue transglutaminase (tTG) and human leucocyte antigen (HLA)-DQB1 alleles was tested in Down's syndrome (DS) patients with and without coeliac disease (CD). Immunoglobulin A (IgA) and G (IgG) anti-tTG were measured in radioligand binding assays and compared with conventionally analysed IgA antibodies against gliadin (AGA) and IgA autoantibodies against endomysium (EMA) in 48 DS patients. HLA-DQB1 typing was carried out by polymerase chain reaction and hybridization with allele-specific probes in 41/48 patients. Both IgA-tTG and IgG-tTG, as well as EMA, were detected in 7/48 and AGA in 15/48 patients. Intestinal biopsy showed histopathological changes consistent with CD in 9/16 patients. HLA-DQB1 typing, available for 8/9 patients with and for 33/39 without CD, demonstrated that 5/8 with CD had DQB1*02 compared with 7/33 of those without ( p = 0.0345). In patients with anti-tTG, 5/6 had the DQB1*02 allele compared with 7/35 of those without ( p = 0.0053).

Conclusions: Anti-tTG are HLA-DQB1*02-associated autoantibodies which together could be useful screening tests for silent CD in DS patients. In patients with gastrointestinal symptoms or clinical signs of malabsorption, anti-tTG should be combined with AGA to detect other forms of enteropathies and CD.     

HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children

The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLADQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMApositive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.     

Assessment of the DQ heterodimer test in the diagnosis of celiac disease in the Canary Islands (Spain)

BACKGROUND: Celiac disease is a multifactorial disorder of the proximal small intestine associated with a permanent intolerance to gluten. The HLA-DQ(alpha1*0501, beta1*02) heterodimer is strongly associated with this disease. MATERIALS AND METHODS: The authors studied a sample of 354 unrelated Caucasoid individuals: 118 patients with celiac disease and 236 control subjects. All patients and controls subjects were born in Gran Canaria (Canary Islands) at least two generations ago.The authors typed the HLA-DQA1 and DQB1 genes by DNA methods. The positive and negative predictive values of the test were studied. RESULTS: The mean age at diagnosis was 25.4 months, with a statistically significant proportion of females (64.4%, P < 0.002). For DQB1 gene, the susceptibility allele found was DQB1*02 (relative risk [RR] = 7.60, confidence interval [CI]: 5.35-10.78), whereas for the DQA1 gene, the susceptibility alleles found were DQA1*0501 (RR = 2.99, CI: 2.16-4.14) and DQA1*0201 (RR = 1.88, CI: 1.25-2.82). The presence of the DQ(alpha1*0501, beta1*02) heterodimer was strongly associated with the disease (92.4% in the patients group vs. 21.6% in control subjects). HLA-DQ8 heterodimer was absent in the authors' patients. DQB1*02 homozygous subjects presented a higher relative risk for celiac disease. There was no correlation of DQB1*02 dosage with age at onset below 12 years of age or with gender distribution. Sensitivity, specificity, and the positive and negative predictive values of the test were 92.4%, 78.4%, 68.1%, and 95.4%, respectively. CONCLUSIONS: The presence of the DQ2 (DQA1*0501/DQB1*02) heterodimer is strongly associated with celiac disease in the population studied by the authors. The value of this test derives from its ability to exclude disease when a negative result occurs.     

Sleep characteristics in children with Down syndrome.

BACKGROUND: Obstructive sleep apnea syndrome is common in children with Down syndrome (DS). Little is known about sleep patterns, especially arousals, awakenings, and movements during sleep in children with DS. OBJECTIVE: To determine the characteristics of sleep disorders in children with DS and to define the associations between respiratory disturbance and arousals, awakenings, and movements. METHODS: The study included 23 children with DS, compared with 13 children with primary snoring. All underwent a 6- to 8-hour sleep study. RESULTS: The respiratory disturbance index was significantly higher in the children with DS (2.8 +/- 2.3 events/h vs 0.6 +/- 0.4 events/h; P <.05). Sleep was significantly fragmented in children with DS, who had a significantly higher arousal/awakening (A/Aw) index (24.6 +/- 7.9 events/h) compared with the comparison group (17.6 +/- 4.0 events/h) (P <.02). A higher percentage of jerks associated with A/Aw and respiratory event-associated A/Aw was observed in patients with DS (45.2% +/- 25% and 8.6% +/- 6.4%, respectively) compared with the control patients (10.2% +/- 4.5% and 1.5% +/- 2.1%) (P <.02). The median length of occurrences of stage 2 sleep was 27% shorter in the DS group (P <.03). The number of shifts from "deeper" to "lighter" stages of non-rapid eye movement sleep was 30% greater (P <.02) in the DS group. CONCLUSION: Children with DS have significant sleep fragmentation, manifested by frequent awakenings and arousals, which are only partially related to obstructive sleep apnea syndrome.     

Prevalence of Celiac Disease in Indian Children with Down Syndrome and its Clinical and Laboratory Predictors

Objective

To study the prevalence of celiac disease in Indian children with Down syndrome and evaluate its clinical and laboratory predictors.

Methods

Prevalence of celiac disease (CD) was assessed in 100 patients with Down syndrome (DS) attending pediatric genetic clinic at All India Institute of Medical Sciences,in a prospective observational study, based on the characteristic symptomatology, positive indirect immunofluorescence anti endomyseal antibody(anti EMA) test and duodenal histology based on adapted Marsh criteria. Clinical and laboratory features were compared in children having both CD and DS and those with DS alone.

Results

Anti EMA was positive in 7 out of 100 patients screened for CD; 6 in whom the duodenal biopsy could be done showed histopathological features consistent with celiac disease. Amongst various clinical features evaluated as possible risk factors; pallor reached statistical significance (OR?=?7.04 95%CI 1.08–45.7). In addition anemia (Hb <11 g%) was significantly associated with CD (p?=?0.06).

Conclusions

The present results showed a high prevalence of CD in DS children in a tertiary hospital in India and low hemoglobin to be an important risk factor. The authors recommend that all Indian children with Down syndrome, particularly those with anemia should be screened for celiac disease.     

Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies

The usefulness of antigliadin (AGA) and antiendomysium antibodies (EMA) as a screening test for coeliac disease (CD) in 113 Down syndrome (DS) patients (61 children) was evaluated. AGA IgA were present in 22.1%, AGA IgG in 48.6%, EMA in 6.2%. Four symptomatic patients, AGA- and EMA-positive, were affected by CD (3.5%). In three AGA- and EMA-positive subjects, permission for intestinal biopsy was refused, while in two AGA-positive and EMA-negative children, the intestinal mucosa was normal. Our study confirms the association of CD and DS, and suggests the usefulness of EMA determination as a test for selecting DS patients for intestinal biopsy.     

High prevalence of coeliac disease in siblings of children with type 1 diabetes

Coeliac disease has been shown to occur more frequently among first-degree relatives of diabetic patients than in the general population. Our objective was to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in determining the genetic susceptibility to coeliac disease (CD) in these subjects. We investigated 240 siblings of diabetic children from 213 families (125 males and 115 females, aged 12.6±4.9 years, mean ± SD). All subjects were tested for the total IgA level to exclude IgA deficiency, and for endomysium IgA to disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead. Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA-DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in 9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six children, two had a normal mucosal finding and one refused the biopsy. The HLA-DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than in siblings without EMA (33%), corrected P =0.031. Conclusion:The 3.8% frequency of coeliac disease found in siblings of diabetic children is close to the 4.3% found previously in Czech children with type 1 diabetes mellitus and is substantially higher than the rate in the healthy children population.     

Can zinc deficiency be used as a marker for the diagnosis of celiac disease in Turkish children with short stature?

BACKGROUND: It is generally accepted that celiac disease (CD) must always be considered when dealing with growth failure in children. Therefore, it is important to develop screening tests for detecting patients that need an intestinal biopsy. The aim of the present study was to investigate the value of plasma zinc levels for the diagnosis of monosymptomatic CD in short-statured children. METHODS: Fourty-nine children with a short stature and 34 healthy controls were investigated. Plasma zinc levels were assayed by atomic absorption spectrophotometry in short-statured children and controls. All patients with short stature underwent endoscopic small intestinal biopsy. RESULTS: Duodenal mucosal histopathology was normal in 25 children. Low plasma zinc values were observed in 54.2% of patients with CD, 32.0% of patients with idiopathic short stature and 14.8% of controls. The mean values of plasma zinc levels were not significantly different among the three groups. Sensitivity, specificity and the positive and negative predictive values for plasma zinc were 45.8, 76.0, 64.7 and 59.4%, respectively. CONCLUSIONS: These results indicate that zinc deficiency is an important problem in CD children with short stature; however, plasma zinc levels are not useful as a screening test for selecting patients for jejunal biopsy.     

Screening frequency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus--data from a German/Austrian multicentre survey

Objective: Type 1 diabetes mellitus (T1DM) is associated with other autoimmune diseases such as celiac disease (CD) and Hashimoto thyroiditis. The aim of this study was to evaluate the screening frequency for CD and thyroid antibodies in a multicentre survey. Methods: The Diabetes Patienten Verlaufsdokumentationssystem (DPV) initiative is based on standardized, prospective, multicentre documentation in children and adolescents with diabetes. Data from 31 104 patients <18 yr of age (52% males, mean age 13.1 yr) with T1DM from 177 paediatric centres in Germany and Austria from 1995 until 2007 were analysed. Results: Of 31 104 patients, 16 994 patients (55%) were screened at least once for CD. In 1995, 44% of the patients were screened for CD compared with 68.6% in 2006. Annual screening for CD has also increased (11.9% in 1995 compared with 43.6% in 2006). Eleven per cent of the patients had positive antibodies for CD. Patients with positive antibodies were significantly younger at diabetes onset and had a significantly longer duration of diabetes (p < 0.001). Compared with screening for CD, screening for thyroid antibodies was performed more frequently (at least once in 62% of the patients). Fifteen per cent of the patients had positive thyroid antibodies. Screening for thyroid antibodies also increased from 62.6 to 72.9%, and annual screening frequency increased from 15.9 to 48.9%. Conclusion: Screening for associated autoimmune diseases in children with T1DM has increased during the past decade. Eleven per cent of the patients had positive CD‐specific antibodies, and 15% had positive thyroid antibodies. Screening for thyroid antibodies is performed more frequently than screening for CD.     

Thyroid dysfunction in Down's syndrome and screening for hypothyroidism in children and adolescents using capillary TSH measurement

Thyroid dysfunction is more common in individuals with Down's syndrome (DS) than in the general population, whose clinical features can mask the presenting signs and symptoms of hypothyroidism. Biochemical screening is necessary; however, venepuncture may be difficult. AIMS: To assess the prevalence of thyroid dysfunction in children and adolescents with DS and the feasibility of screening for hypothyroidism using capillary dried blood spot thyroid stimulating hormone (TSH) from infancy. METHODS: 394 children (217 boys, 177 girls) were clinically assessed for thyroid dysfunction and 305 children (aged 4 months to 18.9 years) were screened for hypothyroidism by capillary whole blood TSH sample. RESULTS: Thyroid dysfunction was detected in 4.6%, with 50% unscreened since neonatal screening. Parents reported minimal distress by fingerprick screening. CONCLUSION: DS is associated with an increased prevalence of thyroid dysfunction, particularly in preschool children. Biochemical screening is essential and capillary whole blood TSH sampling for hypothyroidism is feasible, less invasive and acceptable.     

Age and family history at presentation of pediatric inflammatory bowel disease

OBJECTIVES: Young children are thought to be a unique subset of pediatric patients with inflammatory bowel disease (IBD). The authors' objective was to evaluate the differences in initial clinical presentation of young and older children with IBD and to determine whether a positive family history of IBD is associated with the age of presentation. METHODS: The authors reviewed the records of all patients with new diagnoses of Crohn disease (CD) and ulcerative colitis (UC) who presented between July 1996 and July 1999. Initial evaluation included assessment of growth parameters and laboratory values (hemoglobin concentration, platelet count, erythrocyte sedimentation rate, and serum albumin). Inquiry regarding a family history of IBD was made in every patient. RESULTS: There were 153 patients with new diagnoses (82 with CD and 71 with UC), with a mean age of 11.9 years (range, 16 months-18 years). The children with CD had a higher sedimentation rate and platelet count and a lower mean hemoglobin concentration and serum albumin at presentation than did children with UC. Body mass index (BMI) was significantly lower in patients with newly diagnosed CD than in those with UC. The only significant laboratory differences between patients younger than 11 years and those 11 years or older was a higher mean platelet count in patients with CD who were younger than 11 years. Of the younger patients with CD, 41.7% had a positive family history of IBD, which was significantly greater that that found in the older patients with CD. CONCLUSIONS: Except for higher platelet counts, a lower BMI, and a higher frequency of positive family history in young children with CD, there were no significant differences in the presentation of young children with IBD compared with older children.     

Clinical relevance of monosomy 22q11.2 in children with pulmonary atresia and ventricular septal defect

The purpose of our study was to describe the prevalence and the clinical spectrum of monosomy 22q11.2 in a population of patients with pulmonary atresia and ventricular septal defect. We examined all 44 patients with this conotruncal cardiac malformation who presented to our institution from January 1994 until December 1997. The type of collateral lung perfusion was recorded including anomalies of the pulmonary arteries as well as facial and immunological abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was performed using the probes D22S75 and cHKAD26. Statistical differences were evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten children (23%) with major aortopulmonary collateral arteries (group 1). The remaining 13 children (29%) with major aortopulmonary collateral arteries (group 2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for this microdeletion. All children in group 1 had facial anomalies, six had mild immunological abnormalities including decreased CD 4+ or CD 8+ cells. Anomalies of the pulmonary vascular bed were significantly more frequent in children of group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these pulmonary vascular anomalies, corrective surgery had been accomplished in fewer children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in group 2 and 14/21 children in group 3. Conclusion In children with pulmonary atresia and ventricular septal defect, monosomy 22q11.2 is preferentially associated with major aortopulmonary collateral arteries. Due to the higher incidence of pulmonary arterial abnormalities, successful surgical repair will require a different therapeutic approach in most patients with this microdeletion. Received: 3 June 1998 / Accepted in revised form: 11 September 1998     

Prevalence of celiac disease in Brazilian children and adolescents with type 1 diabetes mellitus

OBJECTIVE: A previously unrecognized high prevalence of celiac disease (CD) has been found by screening among European and North American patients with type 1 diabetes mellitus (DM 1). The prevalence of CD among Brazilian children with DM1 is not known. This study was conducted to determine the prevalence of CD in Brazilian children and adolescents with DM 1. METHODS: One hundred and four children and adolescents with DM 1 (52 males and 52 females; age range 22 months - 19 years) and 105 age and gender-matched control participants were screened for CD using the IgA anti-endomysial antibody test (IgA-EmA) and total serum IgA. A small bowel biopsy was performed in all patients with positive IgA-EmA. RESULTS: Nine of 104 diabetic patients (8.7%) had a positive IgA-EmA. Biopsies were normal in four patients, two had partial or subtotal villous atrophy with elevated intraepithelial lymphocyte (IEL) counts, and three showed partial villous atrophy but with IEL counts under the maximum limit adopted (40 IEL/100 enterocytes). EmA-IgA positive patients had mild, non-specific gastrointestinal complaints including dyspepsia, abdominal pain, flatulence and constipation. All control participants had negative results for IgA-EmA. CONCLUSION: The prevalence of CD in a group of Brazilian pediatric DM 1 patients was at least 4.8%, a prevalence comparable to European and North American studies. The high prevalence of CD among DM 1 emphasizes the need for routine screening in all countries including Brazil.     

Frequency of lower respiratory tract infections in relation to adaptive immunity in children with Down syndrome compared to their healthy siblings

Aim: Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS. Methods: The study group consisted of 22 children with DS and 22 of their healthy, age‐range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined. Results: The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4⁺ T lymphocytes, CD4⁺ invariant natural killer (iNKT) cells and regulatory T cells in the DS group. Conclusion: In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs.     

Annual screening detects celiac disease in children with type 1 diabetes

Objective:  To investigate the prevalence of celiac disease (CD) in a cohort of type 1 diabetes mellitus (T1DM) children and adolescents at the time of clinical diagnosis and to evaluate the screening procedure and possible role of human leukocyte antigen (HLA)-DQ during a 5-yr follow-up.
Research design and methods:  The study group was a cohort of 300 newly diagnosed T1DM children and youths younger than 20 yr followed for 5 yr at six clinical centers for pediatric diabetes in the region Skåne in Sweden. Immunoglobulin A endomysium antibodies were used to screen the patients annually to be considered for an intestinal biopsy. All patients were analyzed for HLA-DQA1-B1 genotypes.
Results:  While 0.7% (2/300) already had a diagnosed symptomatic CD, an additional 3% (10/300) had silent CD at the diagnosis of T1DM. During follow-up, another 6% (17/300) developed CD as follows: 10 after 1 yr, 5 after 2 yr, 1 after 3 yr, and 1 after 5 yr. Therefore, the cumulative frequency of CD confirmed by intestinal biopsies was 10% (29/300). HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.
Conclusions:  Our study confirmed the low prevalence (0.7%) of diagnosed symptomatic CD at the time of clinical diagnosis but document by screening an increasing prevalence of silent CD during a 5-yr follow-up to reach an overall prevalence of 10%. We suggest that children with T1DM should be screened for CD at the onset of T1DM and annually for a minimum of at least 2 yr. HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.