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Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia
Author(s) -
Rets Anton,
Clayton Adam L.,
Christensen Robert D.,
Agarwal Archana M.
Publication year - 2019
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.13014
Subject(s) - hemolytic anemia , jaundice , bilirubin , thalassemia , asymptomatic , medicine , immunology , biology
Hereditary hemolytic anemia ( HHA ) is a group of genetically and phenotypically heterogeneous disorders characterized by premature destruction of red blood cells ( RBC s) with clinical manifestations ranging from asymptomatic to marked hemolytic anemia. There are three main categories of HHA : (a) RBC membrane defects; (b) hemoglobinopathies/thalassemias; and (c) RBC enzyme deficiencies. Hyperbilirubinemia is a frequent consequence of hemolytic anemia and can lead to bilirubin‐associated neurotoxicity in neonates and to jaundice, and formation of gall stones in adults. Hyperbilirubinemia can also be caused by impaired bilirubin conjugation due to polymorphisms and mutations in genes involved in bilirubin metabolism (eg, UGT1A1 ). Neonates with HHA and co‐inherited variants impairing bilirubin conjugation are at increased risk of bilirubin‐associated toxicity. Prior to the advent of next‐generation sequencing ( NGS ), molecular diagnosis of these disorders was limited to targeted single gene Sanger sequencing. However, NGS is making its way into the standard diagnostic workup of complex and multigene disorders like HHA . This review will focus on the molecular updates of HHA with particular focus on the neonatal and pediatric population.