ABNORMAL NEWBORN SCREEN IN A WHIM SYNDROME PATIENT

Abstract

Introduction Newborn screen (NBS) for primary immunodeficiency is performed in the vast majority of states. Dried blood spots are collected from infants. The samples undergo quantitative PCR to quantify T cell receptor excision circles (TRECs). This screening detects Severe Combined Immunodeficiency (SCID) as well as hypomorphic mutations in SCID genes, conditions resulting in the arrest of T cell development such as DiGeorge syndrome and conditions presenting with T cell lymphopenia. Case Description A full term infant was born to a mother with known WHIM syndrome. He was admitted to the NICU on his first day of life for fever, tachypnea and hypoxia. Blood and cerebrospinal fluid cultures were negative at 48 hours and the patient's symptoms resolved. Echocardiogram demonstrated patent ductus arteriosus, pulmonary artery stenosis and atrial septal defect versus patent foramen ovale. On NBS TRECs were not detected until 34 cycles of PCR amplification. ALC was 600 cells/microliter. Flow cytometry showed T and B cell lymphopenia. ANC was initially 9,000 cells/microliter in the setting of fever. At 5 months of life ANC was only 32 cells/microliter. Genetic testing performed at the National Institutes of Health confirmed a heterozygous CXCR4 mutation, specifically c.1000C>T (p.Arg334Ter) consistent with WHIM syndrome. Prophylactic antibiotics, replacement immunoglobulin, granulocyte colony-stimulating factor and CXCR4 antagonists are considerations for therapy. Discussion Low TRECs on NBS may be indicative of disease with life-threatening complications. Immunologists should consider WHIM syndrome when evaluating a patient with abnormal TRECs on NBS. Although this condition is rare, this case expands the differential diagnosis of an abnormal NBS.