Biallelic STEAP3 Variant in Neonatal Hemophagocytic Lymphohistiocytosis.

STEAP3 biallelic loss of function: novel neonatal HLH phenotype (vs AD anemia)

Two brothers with unexplained neonatal familial HLH carry biallelic STEAP3 variants, a gene previously associated with autosomal dominant hypochromic anemia. Both patients presented cytopenia and neonatal HLH, significantly expanding the STEAP3 phenotypic spectrum to a severe autosomal recessive form. This discovery also clarifies STEAP3 genetics: heterozygous variants do not induce an erythrocyte phenotype in the general population, but biallelic variants can cause neonatal HLH.

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This report is important for clinicians facing unexplained familial neonatal HLH: biallelic STEAP3 should now be included in the gene panel for analysis. Clarification of the transmission mode (AD for mild anemia, AR for neonatal HLH) is essential for genetic counseling and family screening.

Clinical impact: 2/3 · Evidence quality: 1/3 · Novelty: 2/2 · Sample size: 0/1 · Journal quality: 0/1 → Total: 5/10