New Method Detects Fatal Copper Disorder at Birth

A blood test developed by NIH scientists can detect a rare but deadly genetic disorder called Menkes Disease in newborns. The test may eventually lead to newborn screening to identify affected children before symptoms appear, when treatment is mostly likely to succeed.

Menkes Disease affects about 1 in 100,000 newborns. Children with the condition typically appear healthy at birth but start to show developmental delays at 6 to 8 weeks. The disorder is caused by defects in a gene called ATP7A, which regulates copper levels in the body. Because the gene is on a sex-related chromosome, the condition primarily affects boys. If not treated, children with Menkes Disease suffer irreparable harm to the brain and nervous system and typically die by 3 years of age.

A research team led by Dr. Stephen G. Kaler, clinical director of NIH's National Institute of Child Health and Human Development (NICHD), suspected that early indicators of Menkes Disease might be seen in blood levels of certain neurochemical molecules that are normally regulated by a copper-containing enzyme. Working with scientists at NIH's National Institute of Neurological Disorders and Stroke (NINDS) and the NIH Clinical Center, Kaler and his colleagues measured various neurochemicals in blood samples from 81 infants who were considered at risk for Menkes Disease because of family history or other factors.

As they reported in the New England Journal of Medicine dated February 7, 2008, the researchers found that abnormal neurochemical levels could distinguish the 46 at-risk children who went on to develop Menkes Disease from those who did not.

Among the children who had positive blood tests for Menkes Disease, the researchers identified 12 males who were less than a month old and had no signs of neurological problems. These newborns received injections of a copper-containing drug that's often used to treat older children who have Menkes Disease.

After about 4.5 years, 92% of the treated newborns were still alive. For comparison, the researchers also looked at a previously studied group of 15 infant boys who received the same treatment regimen but beginning after 3 months of age. Only 13% of the boys in this late-treatment group were still alive about 2 years after their diagnosis and treatment.

The scientists noted that the 12 newborns had varying responses to the copper injections. Two of the children developed relatively normally, but the others had different types of developmental impairments. Analysis of each patient's ATP7A gene showed that boys with the best clinical outcomes had mutations that retained a very basic ability to regulate copper.

Kaler and his colleagues are now working to develop a test that health care providers might use to routinely screen newborn males for Menkes Disease.