Blueberry Muffin Syndrome and Hyperleukocytosis in a Newborn: A Diagnostic Challenge

Blueberry muffin syndrome (BMS) in neonates, characterized by widespread nodular lesions, presents diagnostic challenges due to its diverse etiologies. Hyperleukocytosis, with leukocyte counts exceeding 100,000/μL, is a rare phenomenon associated with severe complications in neonates. Congenital leukemia (CL), a rare diagnosis within the first month of life, is linked to high mortality. This case report presents a unique case of BMS with hyperleukocytosis as the initial presentation of CL. A full-term male newborn, born after an uncomplicated pregnancy, except for Kell isoimmunization, with an Apgar score of 9/10, and an irrelevant family history, showed widespread purple nodules consistent with BMS at birth. Laboratory workup revealed mild anemia, hyperleukocytosis with immature granulocytes on peripheral blood (PB) smear, positive direct antiglobulin test, and elevated alanine aminotransferase and lactate dehydrogenase, without hyperbilirubinemia. Empirical antibiotics and hyperhydration were started, and the neonate was transferred to a level 3 neonatal intensive care unit for further evaluation. A comprehensive etiological investigation was conducted, comprising infectious, immunological, metabolic, and neoplastic factors. A skin nodule biopsy revealed an infiltrate of blast cells, indicative of leukemia cutis, and a bone marrow aspirate confirmed acute myeloid leukemia (AML). The patient successfully completed the NOPHO-DBH-2012 chemotherapy protocol at five months and remains in complete remission at nine months. This case report contributes to the literature by highlighting the diagnostic approach and management strategies for CL presenting with BMS and hyperleukocytosis. This case aims to enhance awareness and understanding of BMS as an initial manifestation of CL. Additionally, the challenges of treating leukemia in neonates, coupled with the lack of specific guidelines for this age group, further underscore the complexities in managing such patients.