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Ryoikibetsu Shokogun Shirizu 1998
Review
Topics: Bilirubin; Biomarkers; Carrier Proteins; Diagnosis, Differential; Humans; Hyperbilirubinemia, Hereditary; Prognosis
PubMed: 9645058
DOI: No ID Found -
Postepy Higieny I Medycyny... 1968
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Naika. Internal Medicine May 1971
Topics: Adult; Humans; Hyperbilirubinemia, Hereditary; Liver Function Tests; Male; Menthol; Osmotic Fragility; Sulfobromophthalein
PubMed: 5572498
DOI: No ID Found -
The New England Journal of Medicine Dec 1971
Review
Topics: Adolescent; Adult; Animals; Bile; Bile Pigments; Bilirubin; Biological Transport; Biotransformation; Child; Chromatography, Gel; Disease Models, Animal; Drug Interactions; Female; Haplorhini; Humans; Hyperbilirubinemia, Hereditary; Infant, Newborn; Jaundice, Chronic Idiopathic; Jaundice, Neonatal; Liver; Models, Biological; Pharmaceutical Preparations; Pregnancy; Protein Binding; Rats
PubMed: 5001058
DOI: 10.1056/NEJM197112162852507 -
Pediatrics Nov 2000Breast milk jaundice is a common problem in nursing infants. It has been ascribed to various breast milk substances, but the component or combination of components that...
OBJECTIVE
Breast milk jaundice is a common problem in nursing infants. It has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unknown. During our study of defects of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) in patients with hereditary unconjugated hyperbilirubinemia (Crigler-Najjar syndrome and Gilbert's syndrome) and neonatal hyperbilirubinemia, we encountered a prolonged case associated with breastfeeding; after cessation of breastfeeding, the infant's bilirubin level became normal. Genetic analysis revealed a missense mutation identical to that found in patients with Gilbert's syndrome, which usually causes jaundice after puberty. We analyzed the bilirubin UGT1A1 of infants with prolonged unconjugated hyperbilirubinemia associated with breast milk to ascertain whether genetic factors are involved.
PATIENTS AND METHODS
We analyzed 17 breastfed Japanese infants with apparent prolonged jaundice (total serum bilirubin concentrations above 171 micromol/L [10 mg/dL]) 3 weeks to 1 month after their birth. Except for jaundice, the infants were healthy and did not show evidence of hemolytic anemia, liver dysfunction, or hypothyroidism. After cessation of breastfeeding, the serum bilirubin concentration began to decrease in all cases. When breastfeeding was resumed, serum bilirubin concentration again became elevated in some infants, but the concentration fell to within normal by 4 months of age. We analyzed the polymerase chain reaction-amplified exon, promoter, and enhancer regions of UGT1A1 by direct sequencing.
RESULTS
Sixteen infants had at least one mutation of the UGT1A1. Seven were homozygous for 211G-->A (G71R), which is the most common mutation detected in the East Asian population, and the mutant enzyme had one third of the normal activity. G71R is the most common missense mutation we found in our analyses in Japanese patients with Gilbert's syndrome, and it corresponds to a UGT1A1 polymorphism in the Japanese population (the allele frequency is.16). One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353). We did not detect a homozygous A(TA)7TAA mutation, which was the most common cause of Gilbert's syndrome in European population, in this study of Japanese infants with prolonged hyperbilirubinemia triggered by breast milk.
CONCLUSIONS
The results indicate that defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. The mutations we found were identical to those detected in patients with Gilbert's syndrome, a risk factor of neonatal nonphysiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia.
Topics: Asian People; Bilirubin; Breast Feeding; Female; Gene Frequency; Gilbert Disease; Glucuronosyltransferase; Humans; Hyperbilirubinemia, Hereditary; Infant, Newborn; Japan; Jaundice, Neonatal; Milk, Human; Mutation, Missense; Polymorphism, Genetic
PubMed: 11061796
DOI: 10.1542/peds.106.5.e59 -
Gastroenterology Jun 2014Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in... (Review)
Review
Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development.
Topics: Animals; Bile; Bile Acids and Salts; Biological Transport; Crigler-Najjar Syndrome; Genetic Predisposition to Disease; Gilbert Disease; Hepatocytes; Heredity; Humans; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Liver; Membrane Transport Proteins; Pedigree; Phenotype
PubMed: 24704527
DOI: 10.1053/j.gastro.2014.03.047 -
Ryoikibetsu Shokogun Shirizu 1995
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Medizinische Klinik Feb 1967
Review
Topics: Bilirubin; Cholesterol; Diagnosis, Differential; Hepatomegaly; Humans; Hyperbilirubinemia, Hereditary; Jaundice; Jaundice, Chronic Idiopathic; Serum Globulins; Splenomegaly
PubMed: 4868439
DOI: No ID Found -
Seminars in Liver Disease Nov 1994
Review
Topics: Animals; Bilirubin; Humans; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Liver
PubMed: 7855632
DOI: 10.1055/s-2007-1007329 -
Seminars in Liver Disease Nov 1994
Review
Topics: Crigler-Najjar Syndrome; Gilbert Disease; Humans; Hyperbilirubinemia, Hereditary; Prognosis
PubMed: 7855631
DOI: 10.1055/s-2007-1007328