New gene test detects fatal copper disorder

A test developed by scientists in the US could greatly extend the survival of infants with Menkes disease, a rare, otherwise fatal disorder of copper metabolism. The scientists devised a test to diagnose the condition early, when the chances for successful treatment are greatest. A study appears in the 7 February 2008 New England Journal of Medicine.

Untreated, Menkes disease results in irreparable harm to the brain and nervous system. Treatment consists of injections with a copper-containing drug. Children with Menkes disease typically die during the first decade of life. Previously, there was no blood test for early detection of Menkes disease.

“The study represents an important advance in the diagnosis and treatment of a rare but devastating genetic disorder,” said Duane Alexander, MD, director of the US National Institute of Child Health and Human Development (NICHD), which lead the study. “The laboratory techniques the researchers used to detect Menkes disease eventually may provide the basis for a newborn screening test to identify children with Menkes at birth, so they have the greatest chance to benefit from treatment.”

Stephen G. Kaler, MD clinical director of the NICHD and lead author of the study said the defect, in the gene designated ATP7A, causes abnormally low levels of copper in the brain and liver as well as excessive amounts of copper in the kidneys and intestines. Copper, although only needed in trace amounts, is an essential nutrient that plays a critical role in brain development.

Infants with Menkes disease usually appear normal at birth but start to show developmental delays at 6 to 8 weeks. Affected children may experience seizures and below normal body temperature. Children with Menkes disease also develop distinctive kinky hair, which is steel-colored or colourless and is easily rubbed off the skull.

Dr Kaler explained that copper is needed for the production of myelin, an insulating material that surrounds certain types of brain and nerve cells. The deposition of myelin around brain and nerve cells is nearly completed by age 2, so the disorder can potentially be treated if copper replacement therapy is started soon after birth. Symptoms of Menkes disease do not usually develop until 2 to 3 months of age, but by that time, the copper deficiency has already caused significant brain damage which treatment seems unable to reverse, Dr Kaler said.

The defective gene in Menkes disease is located on the X chromosome. Because males have only one X chromosome, they have only one copy of the ATP7A gene and so are severely affected by the disorder. Females have two X chromosomes. If they have a defective ATP7A gene, they are not severely affected, because their remaining X chromosome usually has a functioning ATP7A gene.

New research into scar-free healing

New research from the University of Bristol shows that by suppressing one of the genes that normally switches on in wound cells, wounds can heal faster and reduce scarring. This has major implications not just for wound victims but also for people who suffer organ tissue damage through illness or abdominal surgery.

Tissue damage triggers an inflammatory response by white cells to protect skin from infection by killing microbes. The same white cells guide the production of layers of collagen. These layers of collagen help the wound heal but they stand out from the surrounding skin and result in scarring. Research by Professor Paul Martin and colleagues at the University of Bristol shows that osteopontin (OPN) is one of the genes that triggers scarring and that applying a gel, which suppresses OPN to the wound, can accelerate healing and reduces scarring. It does this in part by increasing the regeneration of blood vessels around the wound and speeding up tissue reconstruction.

The findings are published by the Journal of Experimental Medicine on 26 January 29\008 in a paper entitled ‘Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring’.

Genetic basis for itchy skin disorder discovered

A breakthrough study, funded by UK charity Action Medical Research, has found new genetic mutations that can cause the skin to itch.

Published 10 January 2008 in the American Journal of Human Genetics the research points to a genetic disorder that directly causes itchy skin. It is the first time a genetic basis has been discovered for itchy skin.

Hundreds of thousands of sufferers around the world suffer from an itchy skin disorder known as primary localised cutaneous amyloidosis (PLCA). A multinational team of dermatologists looked at the inherited form of the disease known as familial primary cutaneous amyloidosis.

The research has shown that mutations in the oncostatin M receptor-beta gene (OSMR) are the cause of this form of the skin disorder. The team has discovered that skin cells with a mutant copy of the OSMR gene respond differently to certain stimulating molecules known as cytokines.

When stimulated with the cytokines oncostatin M or interleukin-31, the mutant skin cells fail to activate a number of anti-inflammatory genes and the result is itchy skin. Professor McGrath, who is also President of the European Society for Dermatological Research added, “This work provides new insight into what can cause itchy skin.

“We now plan to look for abnormalities of this signalling pathway in other itchy skin disorders and, most importantly, to examine how we can develop new treatments for that most common of all skin symptoms, itch.”

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