Mean platelet volume as short-term follow-up biomarker in children with celiac disease

Objective: To assess the mean platelet volume (MPV) as a short-term follow-up biomarker in celiac disease (CD) and to compare it with anti-tissue transglutaminase antibody (TTGA) assay in Indian children. Material and Methods: Newly diagnosed 35 children aged <12 years who were positive for TTGA and further confirmed by intestinal biopsy with histological Grade 2 and 3 based on modified Marsh Classification were enrolled. TTGA, MPV, and clinical parameters were assessed at enrollment and after 3 months of gluten free diet (GFD). Results: Short stature (94.3%) and diarrhea (80%) were the most common presenting features. 33 (94.3%) children were found to have anemia. MPV reduced significantly from 9.28±1.88 fl to 8.55±1.10 fl after 3 months of GFD, (p<0.001). The mean TTG level reduced from 166.80±59.23 U/ml to 86.45±39.67 U/ml (p<0.001) after 3 months of GFD. Conclusion: MPV is one of the biomarkers that can be used to monitor dietary transgressions in CD in short term

Mapping of the benzoate metabolism by human gut microbiome indicates food-derived metagenome evolution

AbstractSodium benzoate is one of the widely used food preservatives and its metabolism in the human body has been studied only with the host perspective. Despite the human gut microbiome being considered as a virtual human organ, its role in benzoate metabolism is yet to be elucidated. The current study uses a multi-omic approach to rationalize the role of human gut microbes in benzoate metabolism. Microbial diversity analysis with multiple features synchronously indicates the dominance of Bacteroidetes followed by Firmicutes, Actinobacteria, and Proteobacteria. Metagenomic exploration highlights the presence of benzoate catabolic protein features. These features were mapped on to the aerobic and anaerobic pathways of benzoate catabolism. Benzoate catabolism assays identified statistically significant metabolites (P &lt; 0.05) associated with the protocatechuate branch of the beta-ketoadipate pathway of the benzoate metabolism. Analysis of the 201 human gut metagenomic datasets across diverse populations indicates the omnipresence of these features. Enrichment of the benzoate catabolic protein features in human gut microbes rationalizes their role in benzoate catabolism, as well as indicates food-derived microbiome evolution.</jats:p

Reliability of coeliac serology in monitoring dietary adherence in children with coeliac disease on a gluten-free diet

This study aimed to determine the utility of coeliac serology for monitoring dietary adherence in coeliac disease. Serum anti-tTg IgA and anti-DGP IgG levels of 42 newly diagnosed patients were measured at diagnosis and at intervals of three, six and 12 months after starting a gluten-free diet. Both anti-tTg and anti-DGP antibodies decreased in all patients. The decline in the former was significantly greater at 3–12 months throughout, while in the latter the decline was seen only at three months but not subsequently. Serial measurement of coeliac serology may help in monitoring adherence to a gluten-free diet. </jats:p

Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers

Background: Biotin is the coenzyme of multiple carboxylases involved in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotinidase (BTD) deficiency is an autosomal recessive disorder affecting the biotin cycle. It disrupts endogenous biotin recycling and results in multiple carboxylase deficiency depending upon the level of enzyme activity. Children with profound deficiency often present in infancy with neurocutaneous manifestations. Management of symptomatic children or screen-positive newborns is lifelong oral supplementation with biotin. There may be partial or complete resolution of symptoms in the former. Clinical Description: We describe two unrelated families diagnosed as profound BTD deficiency, with three affected children in each family. The first family had two symptomatic surviving children, a 2-year-old boy with seizures, developmental delay, and hearing loss, and a 1.5-month-old boy with seizures. Diagnosis was established while ascertaining etiology for seizures refractory to multiple anticonvulsant therapy. The second family was referred for postconceptional counseling following two infantile deaths with similar phenotype, early-onset seizures, encephalopathy, and acute metabolic decompensation. Management: The affected children in the first family showed a dramatic response in seizure controls with oral biotin though the other symptoms such as developmental delay and hearing loss remained unaffected. Mother was advised regarding prenatal diagnosis in the next pregnancy but was unwilling. In the second family, stored genetic material from the earlier affected infant revealed a pathogenic homozygous indel in the BTD gene, which was confirmed in utero in the subsequent pregnancy. Both women were started on oral biotin on the lines of antenatal management of holocarboxylase synthetase deficiency. After birth, therapy was continued on the confirmation of profound BTD deficiency in both babies. They have remained asymptomatic on follow-up; the first baby till a year and the second till 3 months. Conclusion: There is a considerable phenotypic variability in profound BTD deficiency. Early detection and prompt treatment with biotin may result in complete resolution of some symptoms and ameliorate others. Antenatal biotin supplementation in families at high risk or with prenatal diagnosis of BTD deficiency may have a favorable outcome in affected progeny

Utility of human leukocyte antigen DQ2 and DQ8 genotypes in Celiac disease: Two sides of the coin

Human Leukocyte Antigen (HLA) DQ2 and DQ8 are the known risk genotypes for Celiac Disease. Diagnosis of celiac disease requires serology testing and intestinal biopsy however, genetic testing could also be implemented because of its high negative predictive value. Our study, initiated prior to the publication of 2020 guidelines, evaluated the utility of HLA DQ2 and DQ8 genotyping in the cohort of 537 children with celiac disease and their 1420 first-degree relatives. We attempted to evaluate its applicability in low-middle-income countries like India. Prevalence of celiac disease was observed at 18.52% and 15.68% based on serological and histopathological diagnosis in first-degree relatives. HLA DQA1*0501 and DQB1*0201 alleles were the most frequently observed alleles in index cases (84.4% versus 86.4%), biopsy proven first-degree relatives (77.9% vs 72.15) and serology negative first-degree relatives (67.7% vs 58.3%) (p&lt;0.001). A strong association of DQA1*0501 and DQA1*0301 alleles was observed with high serology positivity (p&lt;0.05). The majority of the subjects in our cohort had histopathologic scores of 3c (54.80%), 3b (22.13%), 3a (22%) and grade 2 (1.05%) (p&lt;0.001). HLA DQB1*0201 was observed as 100% in cases with Marsh grade 2, 72.5% in grade 3a, 82.7% in grade 3b and 85.6% in grade 3c (p=0.017) mucosal lesions. HLA DQA1*0501 and DQB1*0201 alleles of the DQ2 genotype also predicted the severity of intestinal mucosal damage assessed by Marsh grading when used in conjunction with anti-tTG-IgA. When performed in-house using polymerase chain reaction-sequence specific primers method, the assay was economical in identification of mucosal severity in index cases and the first-degree relatives. Its value as a model for additive predictive value in the diagnostic algorithm of cases with tTG-IgA less than 10 times of the upper limit of normal needs further evaluation.</jats:p