UNC13D and Encephalopathy: The heterozygous R414L mutation has been described in 2 patients with compound heterozygous mutations in UNC13D with late-onset primary HLH associated with encephalopathy in the context of other typical features of HLH.3 Patients with at least one allele bearing a nonsynonymous rather than a disruptive mutation may develop symptoms at a significantly older age, suggesting that residual degranulation function allows some defensive capacity.7