Vermeulen Marijn J, de Haas Valerie, Mulder Margot F, Flohil Claudie, Fetter Willem P F, van de Kamp Jiddeke M
VU University Medical Center, Department of Neonatology, Amsterdam, The Netherlands.
Eur J Med Genet. 2009 Nov-Dec;52(6):417-20. doi: 10.1016/j.ejmg.2009.07.002. Epub 2009 Jul 10.
Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic heterogeneous autosomal recessive disorder. We report two siblings with FHLH caused by a PRF1 mutation. The first child died in utero with hydrops fetalis and the second presented soon after birth with fatal multiple organ failure. Post-mortem DNA analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in both cases, with their non-consanguineous parents being heterozygous for the same mutation. Review of the literature shows that perinatal presentation of FHLH is rare. Diagnosis is difficult because in most cases histologic examination reveals no hemophagocytosis and the disease is rapidly fatal. The association between hydrops fetalis and FHLH has been reported in four previous reports. We present the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH should be included in the differential diagnosis of non-immune hydrops fetalis and neonatal multiple organ failure.
家族性噬血细胞性淋巴组织细胞增生症（FHLH）是一种具有遗传异质性的常染色体隐性疾病。我们报告了两名因PRF1基因突变导致FHLH的同胞患儿。第一个孩子在子宫内死于胎儿水肿，第二个孩子出生后不久出现致命的多器官功能衰竭。尸检DNA分析显示，两例患儿的PRF1基因均存在纯合的c.666C>A（p.His222Gln）突变，其非近亲父母为该突变的杂合子。文献回顾表明，FHLH的围产期表现较为罕见。诊断困难，因为在大多数情况下，组织学检查未发现噬血细胞现象，且该病进展迅速，常导致死亡。此前有四份报告报道了胎儿水肿与FHLH之间的关联。我们报告了首例经DNA分析确诊的由FHLH引起的胎儿水肿病例。FHLH应纳入非免疫性胎儿水肿和新生儿多器官功能衰竭的鉴别诊断。
