IL-1 blockade as a novel approach to treatment of hyperzincemia and hypercalprotectinemia, a possible new autoinflammatory syndrome

Methods We describe a patient initially evaluated at 10 months of age for gross developmental delay, failure to thrive, splenomegaly, and microcytic anemia. Physical exam was significant for weight <3rd percentile, splenomegaly (down 5cm), and head lag. Initial laboratories revealed microcytic anemia (hemoglobin 8.7 g/dL); elevated platelets 499 K/uL, C-reactive protein 23.2 mg/dL (<0.2) and erythrocyte sedimentation rate 120 mm/h (0-10). Radiographs showed Erlenmeyer flask deformities of the femurs. Workup for lysosomal storage disorders, oncologic processes, and infections were negative. Genetic testing of known mutations in FAS, CIAS1, ELA2, LPIN2, MVK, PSTPIP1, and TNFRSF1A were negative. Immunoglobulins were elevated with normal T and B cells. On further workup for failure to thrive, a plasma zinc level was found elevated at 532 mcg/dL (60-120). Due to his persistently inflamed state, there was concern for hyperzincemia related to hypercalprotectinemia. Calprotectin level, measured by enzyme-linked immunosorbent assay, was elevated: 428,300 ng/mL (<420). On the basis of these findings the diagnosis of hyperzincemia associated with hypercalprotectinemia was made (OMIM 194470). Additionally, the patient’s workup has revealed the following mutations with unknown clinical significance: a heterozygous variant in the MEFV gene (T577A), a hemizygous duplication of exons 61-79 of the dystrophin gene (CPK normal), and a maternally inherited microduplication at Xp21.2. Colchicine was started due to the MEFV gene mutation with little to no improvement. Based on calprotectin’s role in inflammation, and possible link to IL-1, anakinra was initiated.