Aiming for a shorter time to diagnosis: pediatric eosinophilic esophagitis in British Columbia

Longer time to diagnosis for patients with eosinophilic esophagitis can lead to adverse patient outcomes, but the length of diagnostic delay has not been quantified for patients with eosinophilic esophagitis in Canada. Our study defines the time to diagnosis (TTD) for pediatric patients with eosinophilic esophagitis in British Columbia and identifies factors that predict increased time to diagnosis. The median TTD was 21 months (1.75 years; IQR = 7, 45) with a median age at EoE diagnosis of 105 months (8.75 years; IQR = 44, 156). Caucasians experienced significantly longer TTD compared to other ethnicities (24 months (IQR = 7, 52) and 12 months (IQR = 4.5, 23) respectively, p = 0.008). Caucasian ethnicity (p = 0.037) and older age at the time of diagnosis (p = 0.006) predicted increased TTD. Our model explained 7.9% (Adjusted R² = 0.079) of the total variance for our cohort.Medicine, Faculty ofOther UBCNon UBCAllergy and Immunology, Division ofGastroenterology, Division ofMedicine, Department ofPediatrics, Department ofReviewedFacult

A CARD9 polymorphism is associated with decreased likelihood of persistent conjugated hyperbilirubinemia in intestinal failure.

Recently, genetic associations have been described in intestinal transplants. Namely, Crohn's disease susceptibility gene NOD2 polymorphisms have been reported to be more prevalent in patients with graft failure following intestinal transplantation (IT). Therefore, we sought to determine if polymorphisms in the NOD2 signaling cascade, including NOD2, CARD9, RAC1 and ATG16L1 are associated with intestinal failure (IF) or its complications. We carried out a cross-sectional study of 59 children with IF and 500 healthy Caucasian controls. Using the Taqman platform we determined the prevalence of NOD2 as well as ATG16L1, RAC1 and CARD9 SNPs. NOD2 pathway polymorphisms were evaluated in relation to outcomes of episodes of sepsis, ICU admissions, hyperbilirubinemia and need for IT. We found that the minor allele of a CARD9 SNP was associated with protection from developing IF when compared to healthy controls and was also associated with decreased odds of sustained conjugated hyperbilirubinemia. Therefore, IF patients with CARD9 polymorphism are less likely to develop progressive liver disease and suggests that host innate immunity may play a role in IF associated liver disease

Clinical characteristics of study population.

<p>Clinical characteristics of study population.</p

Frequency of clinical outcomes.

<p>Frequency of clinical outcomes.</p

Genetic analysis of the frequency of minor allele of NOD2, CARD9, RAC1 and ATG16L1 polymorphisms in IF patients with conjugated hyperbilirubinemia (CB≥50 µmol/L).

*<p>: P_adj are the genetic association analysis p-values from the multivariate analysis.</p

Genetic analysis of the frequency of minor allele of NOD2, CARD9, RAC1 and ATG16L1 polymorphisms in IF patients with conjugated hyperbilirubinemia (CB≥100 µmol/L).

*<p>: P_adj are the genetic association analysis p-values from the multivariate analysis.</p

Genetic analysis of the frequency of minor allele of NOD2, CARD9, RAC1 and ATG16L1 polymorphisms in patients and controls.

<p>Genetic analysis of the frequency of minor allele of NOD2, CARD9, RAC1 and ATG16L1 polymorphisms in patients and controls.</p

Exome sequencing enables diagnosis of X-linked hypohidrotic ectodermal dysplasia in patient with eosinophilic esophagitis and severe atopy

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical and genetic heterogeneity between different ectodermal dysplasia types and evidence of incomplete penetrance and variable expressivity increase the potential for misdiagnosis. We describe a family with X-linked hypohidrotic ectodermal dysplasia (XLHED) presenting with variable expressivity of symptoms between affected siblings. In addition to the classical signs of hypohidrosis, hypotrichosis and hypodontia, the index patient—a 5 year old boy, also presented with a severe atopy phenotype that was not observed in the other two affected brothers. Exome sequencing in the index and the mother identified a pathogenic nonsense variant in EDA (NM_001399.4: c.766 C>T; p. Gln256Ter). This study highlights how exome sequencing was crucial in establishing a precise molecular diagnosis of XLHED by enabling us to rule out other differential diagnoses including NEMO deficiency syndrome, that was initially presented as a clinical diagnosis to the family.Medicine, Faculty ofOther UBCNon UBCAllergy and Immunology, Division ofDermatology and Skin Science, Department ofGastroenterology, Division ofMedical Genetics, Department ofMedicine, Department ofPediatrics, Department ofReviewedFacult