Methods: Whole exome sequencing (WES) for patient and parents was performed. Clinical course and immunophenotyping were reviewed.
Results: Hepatosplenomegaly, hepatic calcifications and large placenta were noted on prenatal ultrasound at 35 weeks performed for maternal pre-eclampsia. Postnatal evaluation revealed thrombocytopenia and direct hyperbilirubinemia, raising concerns for congenital infection, chromosomal abnormality, or a metabolic disorder. However, the abnormalities normalized over 7 days and he had a negative congenital infection work up, and karyotype, microarray, and metabolic evaluation were normal. WES showed a single likely pathogenic variant, a de novo c.1021_1022delAA; p.Asn341Tyr-fs*8 hemizygous deletion in XIAP, predicted to be null. Flow cytometry revealed <1.5% XIAP expression in all peripheral blood mononuclear lineages. After hospitalization at 10 mo for fever and hives, IgG and prophylactic medications were started. At 14 mo he was again hospitalized for fever, neutropenia, and elevated ferritin that spontaneously resolved. Otherwise, his development is progressing normally and HCT is planned.
Conclusions: XIAP deficiency presented with prenatal hepatic inflammation and newborn findings mimicking congenital infection. Fever, hives and incomplete HLH occurred before 15 mo. The early diagnosis of XIAP deficiency has allowed for definitive HCT to be undertaken electively.