Menkes Disease

Menkes disease is a disorder caused by a mutation of the ATP7A gene. This ATP7A gene affects how the body transports copper and maintains copper levels.

What Is Menkes Disease?

Copper is an essential mineral that our bodies use in many ways. While the body only uses a small amount of copper, even this tiny amount is required for many functions. Copper helps with metabolism, brain functioning, blood vessel and blood cell formation, wound healing and the immune system. Copper also helps to convert iron into a usable form in the body. It is naturally available in many foods and dietary supplements.

Menkes disease, also known as Menkes syndrome, is a disorder caused by a mutation of the ATP7A gene. This ATP7A gene affects how the body transports copper and maintains copper levels.

Menkes disease occurs mostly in male infants and is characterized by coarse, kinky hair (lead to its nickname of “kinky hair disease”), as well as failure to grow and thrive. Menkes disease is believed to occur in about 1 in 35,000 live male births.

Menkes disease usually causes low copper levels in blood plasma, the liver and the brain. The condition also reduces the activities of copper-dependent enzymes in the body. Copper may accumulate in other tissues, such as the kidney. Because the condition prevents the body from using copper correctly, Menkes disease can lead to serious damage to the brain and nervous system, and can harm a child’s development.

What Are the Symptoms of Menkes Disease?

Menkes disease may not be obvious in infants until two to three months after birth, when signs typically begin to appear. Low copper levels at birth do not necessarily indicate Menkes disease, since many otherwise healthy infants may be born with temporarily low copper levels.

Besides having coarse, twisted hair, infants with Menkes disease may have short, thin hair that is light in color or even white, silver or gray.

Other signs of Menkes disease include:

  • Lack of weight gain
  • Lack of normal growth (failure to thrive)
  • Seizures
  • Lack of muscle development
  • Poor head control
  • Reduced muscle tone (hypotonia)
  • Sagging cheeks
  • Abnormal development of the sternum and rib cage (pectus excavatum)
  • Low body temperature (hypothermia) in the newborn period
  • Intellectual disability in older children

Rarely, an infant with Menkes disease may have a milder form of the condition with less severe symptoms presenting later in childhood.

How Is Menkes Disease Diagnosed?

The first step in diagnosing Menkes disease includes a physical exam. This can identify some of the key signs of Menkes disease, such as thin, kinky hair or poor growth.

A pediatrician or other health care provider may order blood tests or genetic tests to make an accurate diagnosis. For newborns, a diagnostic test known as plasma catecholamine analysis can measure certain natural neurochemicals and help identify the disorder. Genetic testing may also show the ATP7A mutation that causes Menkes disease.

How Is Menkes Disease Treated?

Menkes disease is a rare condition that affects many areas of the body, so collaboration among different specialties is necessary for the best outcomes. These specialties include:

Once diagnosed, Menkes disease can be treated with copper supplements, delivered by daily subcutaneous injections. However, results can vary depending on the type of copper complex used and the severity of the ATP7A mutation.

For example, children whose bodies can still transport some amount of copper are most responsive to copper histidinate (CuHis) treatment. This can improve their growth, overall survival and neurological development, and reduce occurrence of epilepsy.

Because it is a complex, rare disease that affects nearly all areas of the body, treatment of Menkes disease comes with significant challenges. This includes diagnosing Menkes disease and starting treatment as soon as possible, within 28 days of birth. Also, because copper is vital to a developing nervous system, any treatment for Menkes disease must be able to cross the blood-brain barrier.

Researchers are also working to improve newborn screening for Menkes disease.

What Are the Long-Term Consequences of Menkes Disease?

Without treatment, most Menkes disease patients do not survive past age 3. Early diagnosis and treatment can vastly improve a child’s survival and symptoms.

Next Steps

If you or your pediatrician suspect that your child has Menkes disease, it is important to consult an experienced physician as soon as possible.

Nationwide Children’s Hospital, one of the top pediatric medical centers in the United States, is home to The Menkes Disease Clinic. Nationwide Children's is based in central Ohio, within the nation’s heartland, and is easily accessible by car or airplane, thanks to its location near major U.S. highways and an international airport.

We are proud to offer the expertise of Stephen G. Kaler, MD, MPH, an authority on Menkes disease. Dr. Kaler is a professor of Pediatrics and Genetics and a physician-scientist in the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children's Hospital. He is triple-certified (Clinical, Biochemical and Molecular Genetics) by the American Board of Medical Genetics.