Familial hemophagocytic phohistiocytosis induced by PRF1 mutation with neurologic manifestations as the initial clinical presentations: A case report.

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.