Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis.
We report a novel glucose-6-phosphate dehydrogenase (G6PD) mutation, which we propose to name G6PD Cincinnati (c.1037A > T, p.N346I), found in combination with G6PD Gastonia (c.637G > T, p.V213L) in an infant who presented with neonatal cholestasis. The G6PD Cincinnati mutation results in a non-conservative amino acid substitution at the tetramer interface disturbing its formation, as seen by native gel electrophoresis and immunoblotting. G6PD Gastonia disrupts dimerization of the enzyme and by itself causes chronic non-spherocytic hemolytic anemia. The G6PD Cincinnati mutation may have aggravated the clinical picture of G6PD Gastonia with the result of severe perinatal hemolysis causing cholestasis and associated liver injury.
Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Benjamin
B
Mizukawa
Alex
A
George
Suvarnamala
S
Pushkaran
Lana
L
Weckbach
KarenAnn
K
Kalinyak
James E
JE
Heubi
Theodosia A
TA
Kalfa
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002779:Cholestasis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004247:DNA / Q000235:genetics; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D004247:DNA; D005954:Glucosephosphate Dehydrogenase