BackgroundNewborn screening for severe combined immunodeficiency (SCID) using T cell receptor excision circles (TRECs) enables early detection of disorders affecting T cell development. While low TRECs typically indicate T cell lymphopenia due to primary immunodeficiency, other rare congenital or genetic conditions may also present with abnormal results. Fanconi anemia typically presents with a combination of progressive bone marrow failure, congenital physical abnormalities such as short stature, abnormal skin, and skeletal malformations, especially of the thumbs and forearms, and increased cancer risk, but the clinical spectrum is highly variable.Case PresentationA 2-week-old female was seen in the immunology clinic due to abnormal newborn TRECs screening. The infant was born at 37 weeks to non-consanguineous parents after a pregnancy complicated by maternal anemia and fetal intrauterine growth restriction (IUGR). Family history includes a maternal second cousin who has short stature and absent thumbs. The infant’s parents and siblings were healthy. She had a normal physical exam, including the absence of skin lesions, microcephaly, or skeletal abnormalities. Her initial laboratory values included reduced WBC 4.61 x10e3/uL, reduced absolute neutrophil count (ANC) 1,040/ul. The remainder of her complete blood count (CBC) was normal. Lymphocyte subset analysis revealed absolute CD3 count 1,018 (62%), CD4 count 622 (38%), CD8 count 369 (22%), CD19 count 397 (24%), CD16/56 count 490 (22.3%). The patient's genetic testing revealed a homozygous pathogenic variant in FANCD2 (c.2444 G>A), consistent with the diagnosis of Fanconi anemia (FA-D2).DiscussionFanconi anemia and other inherited bone marrow failure syndromes typically do not present with isolated T cell lymphopenia in the neonatal period, and their cytopenias often develop later in childhood. To our knowledge, this is the first report of Fanconi anemia being detected by newborn screen for SCID. Early diagnosis allows for surveillance for progressive bone marrow failure and malignancy.ConclusionThis case highlights the value of obtaining genetic testing early in the evaluation of an infant with lymphopenia. Early diagnosis allows for anticipatory guidance, multidisciplinary management, surveillance for hematologic complications and family counseling regarding genetic risks.
Chervinskiy et al. (Fri,) studied this question.