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Zhonghua Gan Zang Bing Za Zhi =... Apr 2024To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1...
To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using (2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using -test. 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (=0.652, =0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (=10) and TA7/TA7 (=14) mutations were statistically significant in TBil (=2.143, =0.043). The c.211G>A (p.G71R) heterozygous (=9) and isolated (=15) mutation had no statistical significance in TBil (=0.382, =0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (=270.992, <0.001). There was no statistically significant difference ((2)=3.317, =0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.
Topics: Humans; Glucuronosyltransferase; Mutation; Retrospective Studies; Phenotype; Genotype; Hyperbilirubinemia, Hereditary; Bilirubin; Male; Female; Exons; Adult
PubMed: 38733189
DOI: 10.3760/cma.j.cn501113-20230830-00081 -
Annals of Cardiac Anaesthesia Jan 2024
Topics: Humans; Tricuspid Valve; Perioperative Care; Heart Valve Prosthesis Implantation; Gilbert Disease; Male; Tricuspid Valve Insufficiency
PubMed: 38722133
DOI: 10.4103/aca.aca_58_23 -
Hematology (Amsterdam, Netherlands) Dec 2024Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by gene mutation. CDA Ⅱ is often misdiagnosed as a...
BACKGROUND
Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis.
METHODS
We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing.
RESULTS
Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the *6 allele, consistent with GS.
CONCLUSION
Identification of the novel splice variant in this study further expands the spectrum of known gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.
Topics: Humans; Anemia, Dyserythropoietic, Congenital; Male; Vesicular Transport Proteins; Gilbert Disease; RNA Splicing; Mutation
PubMed: 38655690
DOI: 10.1080/16078454.2024.2343163 -
Viruses Mar 2024Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the... (Review)
Review
Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively.
Topics: Female; Humans; Adolescent; Epstein-Barr Virus Infections; Acalculous Cholecystitis; Herpesvirus 4, Human; Gilbert Disease; Ascites
PubMed: 38543828
DOI: 10.3390/v16030463 -
The American Journal of Case Reports Mar 2024BACKGROUND In the absence of liver transplantation, the natural history of acetaminophen-induced liver failure is characterized by a progressive increase of liver...
BACKGROUND In the absence of liver transplantation, the natural history of acetaminophen-induced liver failure is characterized by a progressive increase of liver function tests, including bilirubin mainly as its conjugated form. The presence of high levels of unconjugated bilirubin is more unusual; its etiology is unclear and its prognostic factor has been poorly investigated. CASE REPORT A 52-year-old man with a history of chronic analgesics, alcohol, and illicit drug abuse developed acute liver failure in relationship with the ingestion of largely supra-therapeutic doses of acetaminophen over the days preceding admission. The patient received the classical N-acetylcysteine treatment regimen for acetaminophen overdose. Clinical course was characterized by a progressive worsening of the neurological condition, evolving to grade IV encephalopathy. Coagulation disorders persisted, with factor V level <10%. He fulfilled the criteria for liver transplantation, but this option was rejected after a careful psychiatric evaluation. Laboratory investigations revealed a progressive increase in serum unconjugated bilirubin until his death. As evidence for hemolysis was lacking, acquired deficit in bilirubin glucuronidation appeared likely and diagnosis of Gilbert's syndrome was excluded. CONCLUSIONS After the exclusion of other causes of high unconjugated bilirubin levels, the progressive increase in unconjugated bilirubin can reflect a persistent defect in bilirubin conjugation in relationship with liver centrilobular injury, but the relationship with acetaminophen-glucuronidation is not known and there are insufficient data to affirm that the ratio unconjugated/conjugated bilirubin could be used as a prognostic factor.
Topics: Male; Humans; Middle Aged; Acetaminophen; Hyperbilirubinemia; Gilbert Disease; Liver; Bilirubin; Liver Failure, Acute
PubMed: 38514990
DOI: 10.12659/AJCR.942703 -
Zhonghua Gan Zang Bing Za Zhi =... Feb 2024To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in...
To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children. Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis. Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G > A accounted for 37.5% (6/16), c.1456T > G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( = 5.539, < 0.05), and indirect bilirubin ( = 5.312, < 0.05). However, there was no significant difference in direct bilirubin levels ( = 1.223, > 0.05) and age of onset ( = 0.3611, > 0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T > G homozygous mutations had the highest serum bilirubin levels. The common pathogenic variants of the UGT1A1 gene sequence are c.1456T > G, c.211G > A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.
Topics: Child; Humans; Bilirubin; Crigler-Najjar Syndrome; Gilbert Disease; Glucuronosyltransferase; Hyperbilirubinemia; Mutation; Retrospective Studies
PubMed: 38514260
DOI: 10.3760/cma.j.cn501113-20230115-00030. -
Orphanet Journal of Rare Diseases Mar 2024Recently, the safety and efficacy of gene therapy were evaluated in patients with Crigler-Najjar syndrome (CNS). Although it is a promising curative option for CNS, many...
Recently, the safety and efficacy of gene therapy were evaluated in patients with Crigler-Najjar syndrome (CNS). Although it is a promising curative option for CNS, many doubts still persist about its long-term efficacy and safety. Furthermore, there is a risk of overlooking several unresolved problems still present in current clinical practice. This letter is a call for action on crucial open issues that remain nowadays an unmet need in the management of CNS patients.
Topics: Humans; Crigler-Najjar Syndrome; Emotions; Genetic Therapy
PubMed: 38448957
DOI: 10.1186/s13023-024-03108-x -
Paediatrics and International Child... May 2024The aim of the study was to assess the health-related quality of life (HRQOL) and cognitive function in patients with Crigler-Najjar syndrome (CNS) type I and its impact... (Observational Study)
Observational Study
BACKGROUND
The aim of the study was to assess the health-related quality of life (HRQOL) and cognitive function in patients with Crigler-Najjar syndrome (CNS) type I and its impact on their lives.
METHODS
Twenty-one patients diagnosed with CNS type I aged 1 month to 18 years in the Paediatric Hepatology Unit of Cairo University Children's Hospital were enrolled in this cross-sectional observational study. The patients' health-related quality of life (HRQOL) was assessed using the World Health Organization Quality Of Life BREF questionnaire (WHOQOL-BREF) and the Short Form 36 Health Survey Questionnaire (SF-36). Cognitive function was assessed using the Stanford-Binet Intelligence Scale: Fifth Edition (SB5).
RESULTS
All patients had a history of admission to a neonatal intensive care unit, 17 were managed by phototherapy only and 5 also underwent exchange transfusion. According to the WHOQOL questionnaire, 11 cases (52.4%) had a low QOL score, and 7 of 13 patients had an average score for their total IQ test. Cases with poor compliance to phototherapy had statistically significantly lower QOL scores (=0.001), while, according to the SF36 survey, cases who received exchange transfusion had statistically significantly higher cognitive function (=0.03). There was a positive correlation between the neurological effect as a complication of the disease and poor physical QOL.
CONCLUSION
Paediatric patients with CNS have significantly lower HRQOL, especially physically, psychologically and environmentally. It is recommended that assessment of HRQOL should be a routine part of follow-up in CNS patients. Patients whose HRQOL is affected receive regular psychiatric counselling, social support and rehabilitation. CNS: Crigler-Najjar syndrome; HRQOL: health-related quality of life; IQ: intelligence quotient; NICU: neonatal intensive care unit; QOL: quality of life; SB5: Stanford-Binet intelligence scale: 5th edition; SF-36: Short Form 36 Health Survey Questionnaire; UDGT: uridine diphosphate glucuronosyl transferase; UGT1A1: uridine 5'-diphosphate glucuronosyltransferase; WHOQOL-BREF: World Health Organization Quality of Life Brief Version.
Topics: Child; Humans; Cognition; Crigler-Najjar Syndrome; Cross-Sectional Studies; Quality of Life; Surveys and Questionnaires; World Health Organization; Infant; Child, Preschool; Adolescent
PubMed: 38334259
DOI: 10.1080/20469047.2024.2309727 -
Journal of Human Lactation : Official... May 2024Neonatal jaundice and prematurity pose significant barriers to breastfeeding in the first days of life. There is limited literature exploring the relationship between...
INTRODUCTION
Neonatal jaundice and prematurity pose significant barriers to breastfeeding in the first days of life. There is limited literature exploring the relationship between prolonged jaundice in breastfed infants and Gilbert's (Meulengraght) syndrome. This case study describes the diagnostic and therapeutic challenges associated with Gilbert's syndrome in a late preterm breastfed infant born in Germany.
MAIN ISSUE
In this case report, an infant born to a primipara woman presented at 3 weeks postpartum to an International Board Certified Lactation Consultant. The initial assessment revealed a late preterm infant with inadequate weight gain and jaundice. The dyad received breastfeeding support and eventually achieved adequate weight gain; however, the infant's jaundice persisted.
MANAGEMENT
The consulting midwife suggested that the persistent jaundice was "breastmilk jaundice" and recommended temporarily interrupting breastfeeding. Due to a suspected family history of Gilbert's Syndrome, the dyad was referred, instead, to a pediatric gastroenterologist. Pathologic liver disease was excluded, and genetic testing confirmed Gilbert's Syndrome. At 6 months of age, the dyad was successfully breastfeeding and beginning complementary feeding.
CONCLUSION
Genetic testing for Gilbert's Syndrome should be considered for infants with prolonged jaundice and positive family history. Interruption or cessation of breastfeeding are not evidence-based recommendations, and current guidelines do not support these practices. Lactation professionals play a critical role in the management of breastfeeding for preterm infants with prolonged jaundice and should refer to specialists to rule out pathologic etiologies.
Topics: Female; Humans; Infant, Newborn; Breast Feeding; Gilbert Disease; Infant, Premature; Jaundice; Weight Gain
PubMed: 38334089
DOI: 10.1177/08903344241227226 -
Journal of the American Heart... Feb 2024Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing...
BACKGROUND
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing importance in patients with heart failure; however, their significance in ATTR-CA remains largely unknown. The aims of this study were to characterize the multifaceted nature of ATTR-CA using blood biomarkers and assess the association between blood biomarkers and prognosis.
METHODS AND RESULTS
This is a retrospective cohort study of 2566 consecutive patients diagnosed with ATTR-CA between 2007 and 2023. Anemia (39%), high urea (52%), hyperbilirubinemia (18%), increased alkaline phosphatase (16%), increased CRP (C-reactive protein; 27%), and increased troponin (98.2%) were common findings in the overall population, whereas hyponatremia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in patients with p.(V142I) hereditary ATTR-CA, and became more prevalent as the severity of cardiac disease increased. Multivariable Cox regression analysis demonstrated that anemia (hazard ratio [HR], 1.19 [95% CI, 1.04-1.37]; =0.01), high urea (HR, 1.23 [95% CI, 1.04-1.45]; =0.01), hyperbilirubinemia (HR, 1.32 [95% CI, 1.13-1.57; =0.001), increased alkaline phosphatase (HR, 1.20 [95% CI, 1.01-1.42; =0.04), hyponatremia (HR, 1.65 [95% CI, 1.28-2.11]; <0.001), and troponin-T >56 ng/L (HR, 1.72 [95% CI, 1.46-2.03]; <0.001) were all independently associated with mortality in the overall population. The association between biomarkers and mortality varied across the spectrum of genotypes and left ventricular ejection fraction, with anemia remining independently associated with mortality in p.(V142I) hereditary ATTR-CA (HR, 1.58 [95% CI, 1.17-2.12]; =0.003) and in a subgroup of the overall population with a left ventricular ejection fraction ≤40% (HR, 1.39 [95% CI, 1.08-1.81]; =0.01).
CONCLUSIONS
Cardiac and noncardiac biomarker abnormalities were common and reflect the complex and multifaceted nature of ATTR-CA, with a wide range of biomarkers remaining independently associated with mortality. Clinical trials are needed to investigate whether biomarker abnormalities represent modifiable risk factors that if specifically targeted could improve outcomes.
Topics: Humans; Prealbumin; Cardiomyopathies; Amyloid Neuropathies, Familial; Stroke Volume; Retrospective Studies; Alkaline Phosphatase; Hyponatremia; Ventricular Function, Left; Prognosis; Biomarkers; Anemia; Hyperbilirubinemia; Urea
PubMed: 38314569
DOI: 10.1161/JAHA.123.033094