Familial hemophagocytic lymphohistiocytosis type 2 in a female Chinese neonate: A case report and review of the literature

Abstract

BACKGROUND Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is a rare genetic disorder presenting with fever, hepatosplenomegaly, and pancytopenia secondary to perforin-1 (PRF1) mutation. FLH2 has been described in Chinese but usually presents after 1 year old. We describe a female Chinese neonate with FHL2 secondary to compound heterozygous PRF1 mutation with symptom onset before 1 mo old. We review Chinese FHL2 patients in the literature for comparison. CASE SUMMARY A 15-d-old female neonate was referred to our hospital for persistent fever and thrombocytopenia with diffuse petechiae. She was born to a G5P3 mother at 39 wk and 4 d via cesarean section secondary to breech presentation. No resuscitation was required at birth. She was described to be very sleepy with poor appetite since birth. She developed a fever up to 39.5°C at 7 d of life. Leukocytosis, anemia, and thrombocytopenia were detected at a local medical facility CONCLUSION A literature review identified 75 Chinese FHL2 patients, with only five presenting in the first year of life. Missense and frameshift mutations are the most common PRF1 mutations in Chinese, with 24.8% having c.1349C>T followed by 11.6% having c.65delC. The c.658G>C mutation has only been reported once in the literature and our case suggests it can be pathogenic, at least in the presence of another pathogenic mutation such as c.1066C>T.

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

“…Studies were excluded if they did not discuss nHLH ( n = 280); aggregated nHLH patient data with all ages ( n = 83); provided insufficient detail and/or data describing a case of nHLH ( n = 28); and for other reasons ( n = 8). Two‐hundred‐five cases of nHLH from 142 articles were included in our analysis 12–152 …”

Current genomic diagnostic challenges in Hemophagocytic Syndromes in pediatrics: Case report

“…La variación del punto de acceso en el FHL2 chino se encuentra en la región 2 conservada de la proteína quinasa C, mientras que la reportada en este caso fue una a nivel de la proteína produce el cambio missense de una alanina por valina en el codón 91 (p.Ala91Val), un residuo aminoácido ubicado en el dominio funcional "PERF_HUMAN domain 'MACPF" [21].…”