ABSTRACT
BACKGROUND: The clinical characteristics and gene mutation characteristics of children with Dubin-Johnson syndrome (DJS) need in-depth study. METHODS: The clinical and genomic data of neonatal Dubin-Johnson syndrome (NDJS) and 155 cases with idiopathic cholestasis (IC) were analyzed from June 2016 to August 2020 RESULTS: ABCC2 gene variants were identified in eight patients, including one patient with homozygous variants and seven patients with compound heterozygous variants. A total of 13 different ABCC variants were detected in the NDJS patients, including three nonsense variants, six missense variants, three frameshift variants, and a splice site variant. The variant c.2443C > T (p.R815X), c.4237_4238insCT (p.H1414Lfs*17), c.960_961insGT (p.L322Cfs*3), c.4250delC (p.S1417Ffs*14), c.2224G > A (p.D742N), c.4020G > C (p.K1340N), and c.2439 + 5G > A were not reported in the Human Gene Variant Database. There was no significance in the sex, birth weight, and onset age between the NDJS and IC groups. Compared with the IC group, the NDJS group had significantly higher levels of total bilirubin (TB), but a significantly lower level of alanine transaminase and a ratio of direct bilirubin (DB) to TB. There is no significance in total bile acid, gamma-glutamyl-transpeptidase, albumin, or international normalized ratio between the two groups. CONCLUSIONS: NDJS should be considered in prolonged neonatal intrahepatic cholestasis, especially in infants with normal or slightly elevated transaminase levels. IMPACT: Explore the biochemical parameters, characteristics, and genetic profile of NDJS. By summarizing the characteristics of biochemical indicators, seven new mutation types of the ABCC2 gene were detected, which expanded the mutation spectrum of the ABCC2 gene. NDJS should be considered in prolonged neonatal intrahepatic cholestasis, especially in infants with normal or slightly elevated transaminase levels.
Subject(s)
Cholestasis, Intrahepatic , Cholestasis , Infant, Newborn, Diseases , Jaundice, Chronic Idiopathic , Alanine Transaminase , Bilirubin , Child , Cholestasis/genetics , Cholestasis, Intrahepatic/genetics , Humans , Infant , Infant, Newborn , Jaundice, Chronic Idiopathic/diagnosis , Jaundice, Chronic Idiopathic/genetics , MutationABSTRACT
BACKGROUND: Defects in interleukin 10 (IL10) and its receptors are particularly involved in very early onset inflammatory bowel disease (VEOIBD). However, large fragment deletions of IL10 receptor A (IL10RA) are rare. METHODS: VEOIBD patients with confirmed mutations in the IL10RA gene were enrolled from January 1, 2019 to June 30, 2020. The clinical features and endoscopic-radiological findings of the patients with large fragment deletions of the IL10RA gene were determined and followed up. RESULTS: Thirty-five patients with IL10RA gene mutations, namely, 28 compound heterozygous mutations and 7 homozygote mutations, were enrolled in this study. Six patients carried the reported point mutation c.301C > T (p. R101RW) or c.537 G > A (p. T179T) in one locus and a large fragment deletion in exon 1 in another locus, which were novel mutations in this gene. A 333-bp deletion of exon 1 (117857034-11857366 del) was the main mutation in this locus in 85.7% of the patients with large fragment deletions. The time of disease onset ranged from birth to 4 years, and diarrhea was the main initial symptom. In total, 6/7 patients had perianal complications, including perianal abscess, fistula and skin tags. Six patients accepted thalidomide treatment, 5/7 accepted mesalamine, 3/7 accepted hematopoietic stem cell transplantation (HSCT), and 3/7 were waiting for HSCT. CONCLUSIONS: We identified a novel large deletion of exon 1 involving the IL10RA gene for the first time and showed the characteristics of VEOIBD patients. This study expands the spectrum of Chinese VEOIBD patients with IL0RA gene mutations.
Subject(s)
Inflammatory Bowel Diseases , Receptors, Interleukin-10/genetics , Asian People/genetics , Child , China , Exons/genetics , Humans , Inflammatory Bowel Diseases/genetics , MutationABSTRACT
OBJECTIVE: To study the value of serum gamma-glutamyl transpeptidase (GGT) combined with direct bilirubin (DB) in the diagnosis of biliary atresia. METHODS: A total of 667 infants with cholestasis who were hospitalized and treated from July 2010 to December 2018 were enrolled as subjects. According to the results of intraoperative cholangiography and follow-up, they were divided into biliary atresia group with 234 infants and cholestasis group with 433 infants. The two groups were compared in terms of age of onset, sex, and serum levels of total bilirubin (TB), DB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and GGT. A receiver operating characteristic (ROC) curve analysis was performed for indices with statistical significance, and the area under the ROC curve (AUC) and the optimal cut-off value for diagnosis were calculated. RESULTS: The biliary atresia group had a significantly younger age of onset than the cholestasis group (P<0.001). There were no significant differences in sex, ALT, and AST between the two groups (P>0.05), while the biliary atresia group had significantly higher serum levels of TB, DB, TBA, and GGT than the cholestasis group (P<0.05). GGT combined with DB had the highest AUC of 0.892 (95% confidence interval: 0.868-0.916) in the diagnosis of biliary atresia. At the optimal cut-off values of 324.0 U/L for GGT and 115.1â µmmol/L for DB, GGT combined with DB had a sensitivity of 79.8% and a specificity of 83.2% in the diagnosis of biliary atresia. CONCLUSIONS: GGT combined with DB has high sensitivity and specificity in the diagnosis of biliary atresia and can be used as an effective indicator for diagnosis of biliary atresia in infants.
Subject(s)
Biliary Atresia , gamma-Glutamyltransferase/blood , Alanine Transaminase , Aspartate Aminotransferases , Biliary Atresia/diagnosis , Bilirubin , Humans , InfantABSTRACT
OBJECTIVE: To develop and test the psychometric properties of a responsive feeding questionnaire (RFQ) on the basis of Self-Determination Theory for caregivers of toddlers aged 12-24 months in China. DESIGN: Item generation, preliminary evaluation items, refinement questionnaire, and psychometric properties testing. SETTING: Toddlers' caregivers from Shandong Province, China, were surveyed online between June 2021 and February 2022 (n = 616). MAIN OUTCOME MEASURE: Content, face, and construct validity and reliability of the RFQ. ANALYSIS: Content validity was performed on the basis of expert panel feedback and cognitive interviews among caregivers. Construct validity was evaluated using principal component analysis with varimax rotation. Test-retest reliability was conducted with a sample of 105 caregivers. RESULTS: Over 3 phases of testing, a new instrument was developed to measure responsive feeding in toddler caregivers. The instrument was reliable, with an internal consistency of 0.87 and an intraclass correlation of 0.92. The principal component analysis identified a 3-factor solution (autonomy support, positive involvement, appropriate response) aligning with a theoretical framework from Self-Determination Theory. The final version of the instrument included 23 items. CONCLUSIONS AND IMPLICATIONS: The 23-item RFQ has been validated in a Chinese population. Future research needs to validate this instrument in other countries and with children of different ages.
Subject(s)
Caregivers , Feeding Behavior , Surveys and Questionnaires , Child, Preschool , Humans , Caregivers/psychology , East Asian People , Psychometrics , Reproducibility of Results , Personal AutonomyABSTRACT
RATIONALE: Cholestasis in pediatric patients has diverse etiologies and can be broadly classified as intrahepatic or extrahepatic. The common causes of extrahepatic cholestasis are bile duct calculus, inflammation, or pancreatitis. Malignant tumor is a rare cause of bile ducts obstruction in adolescent. Here we report a 14-year-old male patient with cholestasis due to poorly differentiated adenocarcinoma. PATIENT CONCERNS: A 14-year-old male patient with cholestasis was admitted because of jaundice, weakness, weight loss, and stomach pain for 2 months. The patient had been diagnosed with epilepsy 4 years previously and was being treated with sodium valproate and oxcarbazepine. On admission, laboratory studies showed elevated levels of aspartate aminotransferase (271âIU/L), alanine aminotransferase (224âIU/l), γ-glutamyltransferase (1668.9âIU/L), total bilirubin (66.4âµmol/L), and direct bilirubin (52.6âµmol/L). Additional laboratory tests eliminated common causes of cholestasis such as bacterial/viral infection, autoimmune liver disease, Wilson disease, Alagille syndrome, or progressive familial intrahepatic cholestasis type 3. The results of laboratory investigations showed no improvement after 10 days of treatment with ursodeoxycholic acid and vitamins A, D, and K1. Enhanced magnetic resonance imaging demonstrated a tumor of 22âmm diameter in the duodenal lumen and dilatation of the common bile duct. Endoscopic retrograde cholangiopancreatography detected a tumor in the duodenal lumen. DIAGNOSIS: Considering the clinical features, imaging manifestation, endoscopic findings, and pathologic characteristic, the patient was diagnosed with poorly differentiated adenocarcinoma. INTERVENTIONS: The patient underwent pancreaticoduodenectomy and chemotherapy. OUTCOME: The patient recovered well. Elevated levels of tumor biomarkers or abnormal liver function tests have not occurred during the 2-year follow-up. CONCLUSION: Cholestasis resulting from primary duodenal papillary carcinoma is rare in pediatric patients but should be considered in the differential diagnosis.