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.

Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.