Hyperzincemia and hypercalprotectinemia

Hyperzincemia and hypercalprotectinemia (also known as Hz/Hc syndrome) is an extremely rare autoinflammatory disorder characterized by persistently elevated zinc levels in the blood (hyperzincemia) and markedly increased levels of calprotectin (a calcium- and zinc-binding protein produced mainly by neutrophils and monocytes) in the serum. The condition was first described in the early 2000s and has been reported in only a small number of families worldwide. The elevated zinc in this condition is not due to excessive dietary intake but rather results from dysregulated release of calprotectin from myeloid cells, which binds and carries zinc in the bloodstream. Clinically, patients typically present in early childhood with recurrent infections, hepatosplenomegaly (enlargement of the liver and spleen), anemia, and systemic inflammation. Skin manifestations including dermatitis, as well as failure to thrive, have been reported. Laboratory findings include very high plasma zinc levels (often 3-10 times normal), dramatically elevated serum calprotectin, elevated inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate, and features of chronic inflammation. The condition primarily affects the immune system, liver, spleen, and hematologic system. Treatment is largely supportive and directed at managing symptoms and infections. There is no established curative therapy. Some patients have been treated with immunosuppressive or anti-inflammatory agents with variable success. The condition must be distinguished from other causes of elevated zinc or chronic autoinflammatory syndromes. Genetic studies have linked some cases to dysregulation involving the PRF1 gene or other immune-related pathways, though the precise molecular basis remains under investigation in many families. Long-term prognosis varies, and patients require ongoing monitoring by specialists in immunology and hematology.

Common questions about Hyperzincemia and hypercalprotectinemia