A Case of Hyperzincemia with Functional Zinc Depletion: A New Disorder?

Abstract

We report the case of an 1l-y-old boy with a plasma Zn concentration greater than 200 micromol/L, but with symptoms consistent with Zn deficiency. He has had hepatosplenomegaly, rashes, stunted growth (<3rd centile), anemia, and impaired immune function since infancy. He also has vasculitis and osteoporosis. A plasma Zn-binding protein has been separated and characterized by a combination of size exclusion and ion exchange chromatography and electrophoretic studies and by immunologic methods. Antibodies to the partially purified protein have been raised in rabbits. Size exclusion chromatography shows that Zn is bound to a protein with a mass 110000-300000 kD. Electrophoretic and mass spectrometry studies suggest that the protein may be composed of several subunits. One component of the isolated protein reacts with antiserum to alpha2-macroglobulin; immunoprecipitation studies confirm that the protein is not alpha2-macroglobulin or a histidine-rich glycoprotein. Kinetic studies of zinc metabolism in the patient and his mother with stable Zn isotopes show the presence of increased exchangeable Zn, with a rapid flux from plasma to a stable pool. Liver and muscle Zn and Cu concentrations are raised, but with no abnormal liver histology. Immunoreactive metallothionein in the liver is increased. We suggest that this boy may suffer from a previously unrecognized inborn error of Zn metabolism causing symptomatic zinc deficiency.

The Essential Toxin: Impact of Zinc on Human Health

“…They lead to baseline zinc plasma levels above 300 μg/100 mL, more than three times the physiological level, while iron and copper levels stay normal [171–173]. Even though this exceeds the amount normally found in serum after zinc intoxication, symptoms range from none to severe anemia, growth failure, and systemic inflammation, and resemble zinc deficiency rather than chronic or acute intoxication [172–175]. The elevated zinc levels have been attributed to excessive binding to serum proteins, e.g., by albumin [171,173], or to overexpression of the zinc-binding S100 protein calprotectin [172,174].…”

Severe Anemia and Neutropenia Associated With Hyperzincemia and Hypercalprotectinemia

“…15,16 On the other hand, two sporadic cases of extreme hyperzincemia have been associated with arthritis and pyoderma gangrenosum and with rash, anemia, immune dysfunction, hepatosplenomegaly, and stunted growth. 17,18 Recently Sampson et al described four additional patients, two of them related (mother and son). Biochemical analysis revealed high levels of zinc-binding protein complex and calprotectin (MRP8/14, S100A8/A9 complex).…”

An Assay for Determination of Hepatic Zinc by AAS - Comparison of Fresh and Deparaffinized Tissue

“…An increase in copper and zinc liver concentrations was found in Canadian children with chronic cholestasis (Phillips et al, 1996). Another case report described the increase in zinc concentration in hepatic tissue of a child with hepatosplenomegaly and symptoms of zinc deficiency, and the authors speculated about the existence of a zinc metabolism disorder (Sampson et al, 1997). A study that investigated the concentration of metals in liver tissue of adults with hereditary hemochromatosis found an increase in zinc in the liver parenchyma.…”