Blau syndrome initially manifested with hypercalcemia: a case report and literature review

Blau syndrome, a granulomatous autoinflammatory disease, is a rare condition that is typically characterized by a triad of polyarthritis, uveitis, and dermatitis. It is caused by either an autosomal dominantly inherited or a de novo pathogenic variant in the NOD2 gene. In this report, we present a case of an 11-month-old male with Blau syndrome who presented with calcitriol-mediated hypercalcemia at an early stage. Severe hypercalcemia was controlled by intravenous fluid therapy, diuretics, calcitonin and a short course of corticosteroids. Following resolution of the hypercalcemic episode, the patient gradually developed the full clinical spectrum of Blau syndrome, including symptoms of the classic triad, along with hepatosplenomegaly, lymphadenopathy, and bone marrow involvement. Trio-genome sequencing reported a de novo pathogenic heterozygous variant in the NOD2. Following the genetic testing result, corticosteroids and methotrexate were introduced to control the disease. This is the first reported case of Blau syndrome presenting with hypercalcemia as an initial manifestation, preceding the development of the classic triad of symptoms. This case underscores the importance of considering Blau syndrome in the differential diagnosis of early-onset hypercalcemia of unknown etiology. Molecular genetic testing should be pursued in such cases to facilitate accurate and timely diagnosis, enabling appropriate management.