Copper metabolism and kinky hair.

Roughly 20 years ago, Australian physician David Danks noted a strange similarity between some of his young mentally retarded patients and sheep grazing on copper-poor soils in his native country: Like the abnormal wool of the sheep, the children's hair was short, sparse, lacking in color, and extraordinarily kinky

This led Danks to suspect that his patients' mental deficiencies resulted from a lack of copper. However, much to his dismay, he found that while copper supplements made the animals' wool grow full and thick, adding copper to the children's diets did nothing to benefit them.

Danks' patients had Menkes' syndrome, a fatal inherited disease first described by U.S. neurologist John Menkes. Because his patients did not respond to dietary copper supplements, Danks attributed the disorder to a genetic inability to metabolize copper. Now, three separate research teams report that they have identified the specific gene that when damaged causes Menkes' syndrome.

Researchers expect the discovery of the gene, named MNK, to lead to faster and easier tests for diagnosing Menkes' syndrome in infants suspected of inheriting the rare disorder, which affects roughly one in every 100,000 males worldwide. Affected infants who begin to receive injections of copper solutions soon after birth fail to develop the devastating mental retardation and seizures of Menkes' syndrome, and they also lose the characteristic kinky hair. But current tests for the disorder - which involve measuring copper uptake by patients' connective-tissue cells - require weeks and can only be conducted at a handful of medical centers in the world.

The finding also opens the way for an eventual treatment or cure for Menkes' syndrome through gene therapy. Physicians may one day use viruses to transfer corrected copies of the defective gene responsible for the disorder into the cells of babies with Menkes' syndrome.

The three research teams - led by Seymour Packman of the Howard Hughes Medical Institute at the University of California, San Francisco, Anthony P. Monaco of John Radcliffe Hospital in Oxford, England, and Thomas W. Glover of the Howard Hughes Medical Institute at the University of Michigan in Ann Arbor - report their discovery of the Menkes' syndrome gene in the January Nature Genetics.

Packman's and Glover's groups found that the gene, which lies on the X chromosome, failed to function properly in 23 out of 32 unrelated patients with Menkes' syndrome. Monaco's group found that 16 of 100 such patients lacked portions of the gene.

Moreover, each of the research teams determined that the Menkes' syndrome gene strongly resembles bacterial genes known to transport copper across cell membranes. Copper is an essential trace element for all life forms and is required for the activity of a multitude of body enzymes, including those that produce chemicals vital to communication between nerve cells in the brain, and those responsible for normal hair texture.

The findings "mark a major advance in solving the puzzle of normal copper metabolism," Dean H. Hamer of the National Cancer Institute in Bethesda, Md., comments in an editorial accompanying the three new reports. "One hopes that the availability of the cloned gene will facilitate the development of suitable [diagnostic] assays [for Menkes' syndrome]," he writes.