Abstract
BACKGROUND: To investigate the clinical characteristics of familial hemophagocytic phohistiocytosis (FHL) induced by PRF1 gene mutation and with central nervous injury as the initial presentation. CASE PRESENTATION: Herein, we presented 2 cases of a familial hemophagocytic syndrome caused by PRF1 gene mutation in 1 family with central nervous injury as the first symptom and searched relevant literature for clinical analysis of its pathogenic characteristics. Two children from 1 family were included in this study, both of whom had complex heterozygous mutations of C. 1189_1190dupTG (p.H398Afs*23) and C. 394G>A (p.G132R). Literature search further revealed 20 cases of PRF1 gene mutation-induced familial FHL with central nervous injury as the initial presentation. The main neurological symptoms included cranial nerve injury (81.8%), convulsion (77.3%), ataxia (63.6%), encephalopathy (59.1%), and limb paralysis (40.9%). Cranial imaging findings were dominated by the cerebral hemisphere (100%), cerebellar hemisphere (85%), brainstem (55%), and periventricular white matter (40%), and 73.7% of cases had elevated white blood cell count in CSF. Most cases were confirmed by differential diagnosis and gene sequencing, which suggested that C. 673C>T (P.r225W), C. 394G>A (P.G132r), C. 666C>A (p.H222Q), C. 1349C>T (p.T450M), C. 1349C>T (p.T450M), and C. 443C>C (p.A148G) could be focal mutations of this disease. CONCLUSION: Lesions involving the cerebellum and brainstem in children with ataxia and cranial nerve damage could be indicative of primary FHL; thus, the inherent immune test and gene test should be timely performed to help confirm the diagnosis, guide the treatment, and improve the prognosis.