Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin: further support for existence of a new zinc overload syndrome

Arch Neurol. 2003 Sep;60(9):1303-6. doi: 10.1001/archneur.60.9.1303.

Abstract

Objective: To describe a patient with idiopathic zinc overload without an identifiable source and secondary copper deficiency causing myelopolyneuropathy and pancytopenia.

Design: Case report.

Patient and results: A 46-year-old man presented with severe bone marrow suppression and subsequently developed progressive myelopathy with sensory ataxia. No identifiable cause of myelopathy was detected, and his neuroimaging findings were unremarkable. Plasma analysis demonstrated a low copper level and an increased zinc level (<10 micro g/dL [<12.6-18.9 micro mol/L] and 184 micro g/dL [28.2 micro mol/L], respectively; normal range for both, 80-120 micro g/dL [12.6-18.9 micro mol/L and 12.3-18.4 micro mol/L, respectively) and a low level of ceruloplasmin. There was no evidence for an external source of zinc. Daily oral supplementation with 2 mg resulted in the prompt reversal of hematologic abnormalities, improved but still subnormal plasma copper levels, and normalization of ceruloplasmin values. The patient's neurologic condition deteriorated further, with worsening of myelopathy and development of polyneuropathy. Analyses of plasma copper and zinc levels demonstrated persisting hyperzincemia and subnormal copper levels during 4 years of follow-up. Increased copper supplementation to 8 mg/d partially reversed his neurologic signs. A clinical investigation of 6 siblings and 1 surviving parent did not identify family members with similar abnormalities.

Conclusions: Persistent hyperzincemia without an identifiable external source appears to be a primary metabolic defect, while copper deficiency is a secondary phenomenon, causing hematologic and neurologic abnormalities. Two unrelated patients with similar idiopathic hyperzincemia and hypocupremia have been recently described. This suggests the existence of a new metabolic disorder with idiopathic zinc overload.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Copper / blood
  • Copper / deficiency*
  • Copper / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Pancytopenia / complications*
  • Polyneuropathies / complications*
  • Polyneuropathies / drug therapy
  • Polyneuropathies / metabolism*
  • Spinal Cord Diseases / complications*
  • Spinal Cord Diseases / metabolism*
  • Zinc / blood*

Substances

  • Copper
  • Zinc