Here, we report a highly unusual case of a 5-year-old girl who presented with involuntary movements and an unsteady gait, and was diagnosed with central nervous system isolated HLH (CNS-HLH) by harboring uniparental disomy of a PRF1 mutation (c.1349C > T, p. Thr450Met). The gene discussed is PRF1; the disease is hemophagocytic syndrome.