Korean J Pediatr.  2014 Jan;57(1):50-53. 10.3345/kjp.2014.57.1.50.

A novel PRF1 gene mutation in a fatal neonate case with type 2 familial hemophagocytic lymphohistiocytosis

• Kim JY
• Shin JH
• Sung SI
• Kim JK
• Jung JM
• Ahn SY
• Kim ES
• Seo JY
• Kang ES
• Kim SH
• Kim HJ
• Chang YS
• Park WS

• KMID: 1875961
• DOI: http://doi.org/10.3345/kjp.2014.57.1.50

Abstract

Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC (p.Pro22Argfs*2) and c.1090_1091delCT (p.Leu364Glufs*93). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.

Keyword

FHL2; PRF1; Mutation; Neonate

MeSH Terms

Fever
Flow Cytometry
Frameshift Mutation
Hemodiafiltration
Humans
Infant, Newborn*
Lymphohistiocytosis, Hemophagocytic*
Molecular Biology
Multiple Organ Failure
Perforin
Respiration, Artificial
Perforin