A blended phenotype of primary immunodeficiency and Temtamy syndrome: Dual homozygosity for STK4 and C12orf57 gene variants in a Tunisian infant.

We report a 6-month-old male, born to consanguineous parents, presented with recurrent bronchopneumonia, global developmental delay, and craniofacial dysmorphism. Initial workup revealed profound T-cell lymphopenia and hypoplasia of the splenium of the corpus callosum. Whole exome sequencing (WES) identified two homozygous pathogenic variants: a mutation in C12orf57, diagnostic of Temtamy syndrome, and a mutation in STK4, confirming a primary immunodeficiency. At age 3, the patient developed a life-threatening acute hemolytic crisis with a hemoglobin nadir of 2.3 g/dL. Investigations confirmed cold agglutinin disease, validating the severe immune dysregulation predicted by the STK4 genotype. The patient responded to corticosteroid therapy and is currently awaiting hematopoietic stem cell transplantation (HSCT) from his HLA-compatible father. This report illustrates that early integration of WES in complex pediatric cases is essential to anticipate and manage severe complications, shifting the clinical focus from supportive care to curative interventions like HSCT.