Menkes Syndrome, Canine Copper Toxicosis

Copper (Cu) is an essential nutrient that is required for a broad range of cellular and molecular processes. Mammals have efficient systems to control Cu homeostasis that operate at the level of controlling uptake, distribution, sequestration and excretion of Cu. The study of diseases associated with disturbed Cu homeostasis has greatly enhanced our understanding of the molecular mechanisms involved in Cu metabolism. In man the liver is responsible for excreting excess Cu from the body by means of biliary secretion. Wilson disease is a severe human disorder characterized by Cu accumulation in the liver as a result of a deficiency in biliary Cu secretion.

Menkes disease is an X-linked fatal recessive disorder characterized by neurological deterioration, failure to thrive, peculiar hair and death as a result of genetic mutations. In this condition copper accumulates in some organs (intestine and kidney) and is low in others (liver and brain). The genetic defect leads to both a reduced transport of copper from the intestine into the circulation and into the central nervous system, as well as reduced transport of copper into cells into various copper-dependent enzymes.

Signs and Diagnosis of Menkes Disease

This results in a systemic copper deficiency as well as reduced activity of various copper-dependent enzymes. The reduced activity of these copper-dependent enzymes accounts for most of the characteristic features of Menkes disease patients. The disorder causes severe brain degeneration and arterial changes, resulting in death in infancy. The disease can often be diagnosed by looking at a victim's hair, which appears to be both whitish and kinked when viewed under a microscope.¹

Canine Copper Toxicosis

Canine copper toxicosis is an important inherited disease in Bedlington terriers, because of its high prevalence rate and similarity to human copper storage disease. It can lead to chronic liver disease and occasional hemolytic anemia due to impaired copper excretion. The responsible gene for copper toxicosis in Bedlington terriers has been recently.

References:
1. Aldenhoven M, Klomp LW, van Hasselt PM, de Koning TJ, Visser G.Ned Tijdschr Geneeskd. From gene to disease; Menkes disease: copper deficiency due to an ATP7A-gene defect. 2007 Oct 13;151(41):2266-70