Association of nonimmune hydrops fetalis with familial hemophagocytic lymphohistiocytosis in identical twin neonates with perforin His222Arg (c665A>G) mutation.
BACKGROUND
This is the first study demonstrating that nonimmune hydrops fetalis (NIHF) in identical twin neonates is associated with biallelic gene defect causing familial hemophagocytic lymphohistiocytosis.


METHODS
Preterm male twins (31(4/7) wk) with NIHF and hepatosplenomegaly gradually developed pancytopenia, hyperferritinemia, hyponatremia, hypoalbuminemia, and elevated alanine aminotransferase, aspartate aminotransferase, bilirubin, and lactate dehydrogenase levels. Suspected sepsis led to antibiotic therapy. Upon detection of hemophagocytosis in bone marrow, multiorgan failure and pulmonary bleeding led to death. Homozygous His222Arg (c665A>G) mutation was identified in Perforin.


CONCLUSIONS
Familial hemophagocytic lymphohistiocytosis should be considered in first days of NIHF cases to have chance for HLH-2004 therapy. Missense mutations of Perforin codon His222 may lead to intrauterine presentation.
*Department of Pediatrics, Division of Hematology, Faculty of Medicine, Hacettepe University, Ankara †Department of Pediatrics, Neonatology Intensive Care Unit, Zeynep Kamil Maternity and Children's Education and Training Hospital, Istanbul, Turkey.
Gunay
G
Balta
Sevilay
S
Topcuoglu
Tugba
T
Gursoy
Aytemiz
A
Gurgey
Fahri
F
Ovali
D017809:Fatal Outcome; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics* / Q000503:physiopathology; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000235:genetics* / Q000503:physiopathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020125:Mutation, Missense; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D014430:Twins, Monozygotic
C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin