Dataset Information

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

ABSTRACT:

Objective

Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome.

Materials and methods

Patients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis.

Results

A total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected.

Conclusion

We detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler-Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.

SUBMITTER: Cagan Appak Y

PROVIDER: S-EPMC9131810 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

Çağan Appak Yeliz Y Aksoy Betül B Özyılmaz Berk B Özdemir Taha Reşid TR Baran Maşallah M

Turkish archives of pediatrics 20220501 3

<h4>Objective</h4>Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilb ...[more]

PMID: 35781232

Similar Datasets

Project description:Hypertensive crisis is a medical emergency that can cause acute damage to multiple end-organs. However, relatively little is known on the etiology, treatment, and outcomes of hypertensive crisis in Korean children. The aim of this study was to determine the etiologies and efficacy of drugs for hypertensive crisis in children during the past 5 years at a single center in Korea.We analyzed data from 51 children with hypertensive crisis during the period between January 1, 2010 and April 1, 2014. The patients were divided into two groups: those diagnosed with a hypertensive emergency (hypertension with organ injury, n = 31) and those diagnosed with a hypertensive urgency (hypertension without organ injury, n = 20). Baseline etiologies and risk factors were compared between the two groups. In addition, systolic and diastolic blood pressures were evaluated at 1, 2, 4, and 5 hours after the administration of intravenous antihypertensive drugs.Kidney injury and cancer were the common causes in patients with hypertensive crisis. Cardiovascular complications (cardiac hypertrophy) (p = 0.002), central nervous system complications (p = 0.004), and retinopathy (p = 0.034) were more frequently observed in children with hypertensive emergency than those with hypertensive urgency. However, the proportion of renal complications was similar in both groups. Hydralazine was most commonly used in both groups to control acute increasing blood pressure at first. However, it was often ineffective for controlling abrupt elevated blood pressure. Therefore, intravenous antihypertensive drugs were changed from hydralazine to nicardipine, labetalol, or nitroprusside to control the high blood pressure in 45.1 % of the patients. Particularly, in patients with hypertensive crisis, there was no significant difference in reduction of systolic and diastolic blood pressure and in improvement of clinical outcomes between nicardipine and labetalol administration.Close blood pressure monitoring and careful examinations should be mandatory in children with underlying disease, especially renal diseases and cancer. Furthermore, both nicardipine and labetalol may be effective antihypertensive drug in lowering high blood pressure in children with hypertensive crisis.

Project description:To determine the clinical presentation, diagnostic investigations and laboratory workup done in admitted children with cystic fibrosis at Aga Khan University Hospital Karachi, Pakistan.This is athree years retrospective study from January 2013 to December 2015 conducted at The Aga Khan University Hospital Karachi Pakistan, enrolling admitted patient from birth to 15 years of either gender, diagnosed with CF on the basis of clinical features and positive sweat chloride test. Different clinical presentations were noted including initial presentations. Sweat chloride values more than 60mmol/L were labeled as positive and consistent with diagnosis of CF. Available Delta F-508 mutation analyses were noted. Relevant laboratory and radiological investigations including sputum culture and HR-CT chest findings were documented. Results were analyzed using SPSS version 20.Total 43 children were selected according to the inclusion criteria. Chronic cough (69.76%) was the most common initial clinical presentation. Mean age at onset of symptoms was 14.41± 26.18 months and mean age at diagnosis was 47.20 ± 45.80 months Respiratory features were most common in our cohort including chronic productive cough (90.71%), recurrent bronchopneumonia (72.09%) and asthma like presentation (44.19%) with wheezing and cough. 86% patients presented with failure to thrive. Gastroenterological features including steatorrhea were seen in 55.81% patients and 44.19% patients had abdominal distension. Mean sweat chloride value in our population was 82.70± 22.74. Gene analysis for Delta F-508 was identified in 12 (27.90%) patients. Bronchiectatic pulmonary changes on HRCT were seen in 18 patients (41.86%). Pseudomonas grew in 12 patients (27.90%) in sputum cultures at the time of diagnosis.Respiratory presentations predominate in CF children followed by gastrointestinal features. Nearly half of our patient had bronchiectatic changes on CT scan chest and more than quarter had pseudomonas colonization in the airways at the time of diagnosis. Delta F-508 mutation was found to be uncommon in our study population. There is significant delay in diagnosing patients with CF.

Project description:BackgroundHypertension (HTN), especially masked hypertension, is one of the cardiovascular consequences of nephrotic syndrome. Masked hypertension cannot be identified during routine follow-up visits and adversely effects the patients' cardiac function. The purpose of this study was to use ambulatory blood pressure monitoring (ABPM) to evaluate the blood pressure status of children with nephrotic syndrome.MethodsNinety children with nephrotic syndrome (NS) participated in this cross-sectional study, which was carried out at Cairo University Children Hospital's nephrology clinic (CUCH). A sphygmomanometer was used in the clinic to measure blood pressure, and a Meditech monitor was used for 24-hour ambulatory blood pressure monitoring (ABPM). Interventricular septum (IVS) was measured, and heart functions were evaluated, using echocardiography.ResultsTwo groups comprised the included patients: Group1 (n = 70): HTN group included masked and ambulatory hypertension, and Group 2 (n = 20): non-HTN group included normal blood pressure, white coat HTN and well controlled HTN, 35% of the studied cohort (n = 32/90) had masked HTN.The serum urea was significantly higher in HTN group than non-HTN group with p-value: 0.047, while the serum albumin was significantly lower in HTN group than non-HTN group with p-value: 0.017. The cut-off point of 9.9, the sensitivity and specificity of serum urea to predict the occurrence of hypertension in NS patients was 92.9% and 35% respectively, with p-value : 0.024 and 95% CI (0.534-0.798). The z score of IVS is significantly higher in group 1 (2.5 ± 1.2) when compared to group 2 (1.7 ± 2.1) with p-value: 0.025 and Among group 1, it was noticed that 74% (n = 52/70) of them were systolic non-dipper, also it was observed that the mean serum potassium and cholesterol were significantly higher among systolic non-dipper when compared with systolic dipper patients with p-values: 0.045 and 0.005 respectively.ConclusionChildren with nephrotic syndrome are particularly vulnerable to experience ambulatory hypertension and masked hypertension, which may adversely impact their cardiac condition because they are not detectable by standard blood pressure readings at the clinic.

Project description:Background: Constant cellular damage causes a poor prognosis of hepatitis B virus (HBV) infection. Accumulating evidence indicates the cytoprotective properties of bilirubin. Here, we investigated the association of UDP glucuronosyltransferase family 1 member A1 (UGT1A1), the genetic cause of Gilbert syndrome (GS), a common condition of mild unconjugated bilirubinemia, with HBV infection outcomes. Methods: Patients (n = 2,792) with unconjugated hyperbilirubinemia were screened for HBV infection and host UGT1A1 variations in Ruijin Hospital from January 2015 to May 2023, and those with confirmed HBV exposure were included. The promoter/exons/adjacent intronic regions of UGT1A1 were sequenced. HBV infection outcomes were compared between hosts with wild-type and variant-type UGT1A1. The effect magnitudes of UGT1A1 variations were evaluated using three classification approaches. Results: In total, 175 patients with confirmed HBV exposure were recruited for final analysis. Age, gender, level of HBV serological markers, and antiviral treatment were comparable between UGT1A1 wild-type and disease-causing variation groups. Five known disease-causing mutations (UGT1A1*28, UGT1A1*6, UGT1A1*27, UGT1A1*63, and UGT1A1*7) were detected. The incidence of cirrhosis or hepatocellular carcinoma (LC/HCC) was significantly lower in UGT1A1 variant hosts than in UGT1A1 wild-type hosts (13.14% vs. 78.95%, p < 0.0001). The rarer the UGT1A1 variation a patient possessed, the higher the age at which LC/HCC was diagnosed (R = 0.34, p < 0.05). In contrast, patients without cirrhosis achieving HBsAg clearance were identified only in the UGT1A1 variant group (12.32% vs. 0%). Conclusion: The findings of this study provide insights into the association between preexisting genetically mild bilirubin elevation and viral infection outcome. We showed that the accumulation of UGT1A1 variants or the rarity of the variation is associated with a better prognosis, and the effect magnitude correlates with UGT1A1 deficiency. This study demonstrates the therapeutic potential of host UGT1A1 variations underlying GS against HBV infection outcomes.

Dataset Information

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

Objective

Materials and methods

Results

Conclusion

Publications

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets