Two Different UGT1A1 Mutations causing Crigler–Najjar Syndrome types I and II in an Iranian Family

2015 ◽  
Vol 24 (4) ◽  
pp. 523-526 ◽  
Author(s):  
Yoshihiro Maruo ◽  
Mahdiyeh Behnam ◽  
Shinichi Ikushiro ◽  
Sayuri Nakahara ◽  
Narges Nouri ◽  
...  
Keyword(s):  
Serum Bilirubin ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Compound Heterozygous ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Wild Type ◽  
Iranian Family ◽  
Udp Glucuronosyltransferase

Background: Crigler–Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.Case report: The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2. Results: The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%–36 % of the wild-type. Conclusion: Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2. Abbreviations: CN-1: Crigler–Najjar syndrome type I; CN-2: Crigler–Najjar syndrome type II; GS: Gilbert syndrome; UGT1A1: bilirubin UDP-glucuronosyltransferase; WT: Wild type; TB: total serum bilirubin.

scholarly journals Transcutaneous billirubinometry to estimate total serum bilirubin in neonatal jaundice

2017 ◽  
Vol 57 (1) ◽  
pp. 8 ◽  
Author(s):  
Andra Kurnianto ◽  
Herman Bermawi ◽  
Afifa Darmawanti ◽  
Erial Bahar
Keyword(s):  
Neonatal Jaundice ◽  
Serum Bilirubin ◽  
Subcutaneous Tissue ◽  
Correlation Coefficients ◽  
Total Serum Bilirubin ◽  
Blood Sampling ◽  
Total Serum ◽  
Transcutaneous Bilirubin ◽  
Non Invasive ◽  
Transcutaneous Bilirubinometry

Background The gold standard for diagnosis of neonatal jaundice is total serum bilirubin (TSB) measurement. This method, however, is invasive, painful, and costly in terms of workload, time, and money. Moreover, repeated blood sampling may lead to significant blood loss, which is of particular concern in preterm infants. To overcome these drawbacks, non-invasive methods of bilirubin measurement have been proposed. Transcutaneous bilirubinometry (TcB) determines the yellowness of the subcutaneous tissue of a newborn infant by measuring the difference between optical densities for light in the blue and green wavelength regions.Objective To evaluate the accuracy of transcutaneous bilirubinometry for estimating TSB levels in neonatal jaundice.Methods Subjects were infants aged < 28 days with jaundice who had never been treated with phototherapy or exchange transfusion. The study was done from February to July 2016 in Mohammad Hoesin Hospital. Subjects underwent transcutaneous bilirubin (TcB) and TSB assays, with a maximum interval of 15 minutes between tests.Results One hundred fifty patients were included in this study. The TcB values > 5 mg/dL were correlated to TSB > 5 mg/dL, with 100% sensitivity and 83.3% specificity. This cut-off point was obtained from a receiver-operator characteristic (ROC) curve with AUC 99.3% (95%CI 97.9 to 100%; P< 0.001).The correlation coefficients (r) for TSB and TcB measurements on the forehead were 0.897 (P<0.001).Conclusion Transcutaneous bilirubinometry can be used to accurately estimate TSB levels in neonatal jaundice, and may be useful in clinical practice as a non-invasive method to reduce blood sampling.

Mechanisms of inherited deficiencies of multiple UDP‐glucuronosyltransferase isoforms in two patients with Crigler‐Najjar syndrome, type I

1992 ◽  
Vol 6 (10) ◽  
pp. 2859-2863 ◽  
Author(s):  
Piter J. Bosma ◽  
Jayanta Roy Chowdhury ◽  
Tian‐Jun Huang ◽  
Pulak Lahiri ◽  
Ronald P. J. Oude Elferink ◽  
...  
Keyword(s):  
Type I ◽  
Syndrome Type ◽  
Udp Glucuronosyltransferase

scholarly journals Development of Jaundice Detection Approaches in Neonates

2020 ◽  
Vol 22 (12) ◽  
Author(s):  
Priti Bhagat V ◽  
◽  
Dr Mukesh Raghuwanshi M ◽  
Dr. Kavita Singh ◽  
Dr Sachin Damke ◽  
...  
Keyword(s):  
Clinical Assessment ◽  
Serum Bilirubin ◽  
Visual Assessment ◽  
Assessment Methods ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Gold Standard Method ◽  
Life Detection ◽  
Precision And Accuracy ◽  
Transcutaneous Bilirubinometer

Jaundice is one of the most common diseases that have a significant impact in the first few days of newborn life. Detection and regular monitoring of bilirubin, which is responsible for Jaundice, is an essential phase during the hyperbilirubinemia. In the literature, various clinical assessment methods of Jaundice are available. It motivates us to present a review of these clinical assessment methods in practice, along with their advantages and limitations. In this paper, we have discussed three widely used methods, such as visual assessment, total serum bilirubin and transcutaneous bilirubinometer. From the comparative analysis of these methods, it is concluded that the visual assessment is very subjective in nature, whereas, the total serum bilirubin method is still a gold standard method. The detailed analysis of the methods depicts that the correlation between this two total serum bilirubin and transcutaneous bilirubinometer has enormous potential for improvement resulting in the enhancement in precision and accuracy of bilirubin measurement.

scholarly journals Possible Ibuprofen-Induced Kernicterus in a Near-Term Infant with Moderate Hyperbilirubinemia.

2006 ◽  
Vol 11 (4) ◽  
pp. 245-250
Author(s):  
Peter Gal ◽  
J Laurence Ransom ◽  
Sherri A Davis
Keyword(s):  
Neonatal Intensive Care ◽  
Serum Bilirubin ◽  
Primary Pulmonary Hypertension ◽  
Term Infant ◽  
Auditory Neuropathy ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Albumin Binding ◽  
Unbound Bilirubin ◽  
Near Term

A 36-week gestation newborn was admitted to the neonatal intensive care unit for treatment of primary pulmonary hypertension and possible sepsis. The infant developed hyperbilirubinemia on day 4 of life and peaked on day 5 at a total serum bilirubin of 19 mg/dL. Phototherapy was started on day 4 and continued for 5 days. On day 8 of life, ibuprofen was started for fever; a concurrent total serum bilirubin was 15.7 mg/dL. The subsequent hospital course was uneventful, and discharge occurred on day 22 of life. Because the patient failed a hearing screen at discharge, he was referred for a diagnostic audiology workup. He subsequently failed formal audiometric testing on two occasions one week apart, and was given a diagnosis of auditory dys-synchrony and/or auditory neuropathy, consistent with kernicterus. At 5½ months of age, he was reported to be hypotonic and to have frequent arching movements. Since the total serum bilirubin did not exceed 19 mg/dL, concern was raised that ibuprofen may have caused displacement of bilirubin from its albumin binding site, resulting in kernicterus due to excessive unbound bilirubin concentrations. Ibuprofen should be administered with caution in preterm infants at risk for kernicterus.

Filamin-Associated Dysplasias/Dysostoses and Related Disorders

2018 ◽  
pp. 307-350
Author(s):  
Jürgen W. Spranger ◽  
Paula W. Brill ◽  
Christine Hall ◽  
Gen Nishimura ◽  
Andrea Superti-Furga ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Clinical Findings ◽  
Differential Diagnoses ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Radiographic Features ◽  
Larsen Syndrome ◽  
Otopalatodigital Syndrome

This chapter discusses filamin-associated dysplasias/dysostoses and related disorders and includes discussion on otopalatodigital syndrome type 1, otopalatodigital syndrome type II, Melnick-Needles osteodysplasty, frontometaphyseal dysplasia, boomerang dysplasia/atelosteogenesis type I, atelosteogenesis type III, Larsen syndrome (autosomal dominant), spondylocarpotarsal synostosis syndrome, and Frank-ter Haar syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.

Role of common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of murine mast cells

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2172-2180 ◽  
Author(s):  
Kotaro Suzuki ◽  
Hiroshi Nakajima ◽  
Norihiko Watanabe ◽  
Shin-ichiro Kagami ◽  
Akira Suto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Cytokine Receptor ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Wild Type ◽  
Peritoneal Mast Cells ◽  
The Common

Abstract The regulatory roles of the common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of mast cells were determined using γc-deficient (γc−) and Jak3-deficient (Jak3−) mice. Although the mast cells in γc− and Jak3− mice were morphologically indistinguishable from those in wild-type mice, the number of peritoneal mast cells was decreased in γc− and Jak3− mice as compared with that in wild-type mice. Among γc-related cytokines, interleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the proliferation and survival of bone marrow–derived mast cells (BMMCs) from wild-type mice. However, the effects of IL-4 and IL-9 were absent in BMMCs from γc− and Jak3−mice. In addition, IL-4Rα, γc, and Jak3, but not IL-2Rβ or IL-7Rα, were expressed in BMMCs. In contrast, IL-13 did not significantly induce the proliferation and survival of BMMCs even from wild-type mice, and IL-13Rα1 was not expressed in BMMCs. Furthermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs from wild-type mice but not from γc− and Jak3− mice. These results indicate that γc- and Jak3-dependent signaling is essential for IL-4– and IL-9–induced proliferation and survival of murine mast cells, that the effects of IL-4 are mediated by type I IL-4R and that type II IL-4R is absent on mast cells, and that IL-4 phosphorylates the 65-kd isoform of Stat6 in mast cells in a γc- and Jak3-dependent manner.

scholarly journals Detrimental Effect of Atazanavir Plasma Concentrations on Total Serum Bilirubin Levels in the Presence of UGT1A1 Polymorphisms

2011 ◽  
Vol 56 (3) ◽  
pp. e96-e97 ◽  
Author(s):  
Paola Cicconi ◽  
Teresa Bini ◽  
Alessandra Barassi ◽  
Maddalena Casana ◽  
Olivia Turri ◽  
...  
Keyword(s):  
Detrimental Effect ◽  
Serum Bilirubin ◽  
Plasma Concentrations ◽  
Total Serum Bilirubin ◽  
Total Serum
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