Menkes syndrome
Menkes syndrome is a rare genetic disorder primarily affecting males, caused by mutations in the ATP7A gene located on the X chromosome. This condition leads to impaired copper absorption in the body, resulting in severe neurological and physical symptoms. Children typically begin to show signs of the disease within the first three months of life, which may include developmental delays, seizures, and distinctive hair abnormalities, such as sparse, tangled, and easily broken hair. The incidence of Menkes syndrome varies geographically, occurring in approximately 1 in 50,000 to 250,000 live births in the United States. Most affected children have a life expectancy of only three to five years.
Diagnosis often involves X-rays to examine bone abnormalities and blood tests to assess copper levels. While there is currently no cure, early interventions with copper supplements may offer temporary benefits. Families with a history of Menkes syndrome are encouraged to seek genetic counseling when considering having children, as the disorder follows a typical sex-linked recessive inheritance pattern. Understanding Menkes syndrome can help in recognizing symptoms early and exploring available support options.
Menkes syndrome
ALSO KNOWN AS: Kinky hair disease; steely hair disease; trichopoliodystrophy; X-linked copper deficiency; copper transport disease
DEFINITION Menkes syndrome is an inherited genetic disorder due to an abnormal gene, ATP7A. Menkes syndrome causes impaired copper absorption. This results in arterial changes and deterioration of the brain.
Menkes syndrome is rare. Incidence varies by location; in the United States, it occurs in 1 out of every 50,000 to 250,000 live births. It affects primarily males. Most children born with Menkes syndrome have a life expectancy of three to five years.
Risk Factors
Males are at an increased risk for Menkes syndrome, as are individuals with family members who have this disorder.
Etiology and Genetics
Menkes syndrome is caused by mutations in the ATP7A gene, which is found on the long arm of the X chromosome at position Xq13.2-q13.3. The ATP7A gene specifies a protein called ATPase, copper transporting, alpha polypeptide, which is an essential component of the enzyme that regulates copper levels in the body. Copper is an essential cofactor in several cellular enzymatic processes, but too much of it in the cell can be toxic. One function of the ATP7A protein is to move to the cell membrane to actively eliminate excess copper from the cell. Copper absorption and transport is compromised in a variety of ways in patients with Menkes syndrome, with an accumulation of copper in the kidneys and small intestine and abnormally low levels in the brain. A different mutation in the ATP7A gene that drastically reduces but does not completely eliminate protein function is associated with a variation of Menkes syndrome known as occipital horn syndrome. Physical symptoms are similar but less pronounced.
The inheritance pattern of this disease is typical of all sex-linked recessive mutations (those found on the X chromosome). Mothers who carry the mutated gene on one of their two X chromosomes face a 50 percent chance of transmitting this disorder to each of their male children. Female children have a 50 percent chance of inheriting the gene and becoming carriers like their mothers. In the unlikely event that they live to sexual maturity, affected males would pass the mutation on to all of their daughters but to none of their sons.
Symptoms
Children with Menkes are often born prematurely. Symptoms usually begin to show within three months after birth and may include seizures, brain degeneration and developmental delay, hypotonia (“floppy” muscle tone), hypothermia, osteoporosis, and failure to thrive. Babies with Menkes syndrome often exhibit hair that is stubby, tangled, sparse, lacking in color, and easily broken; chubby cheeks; a flattened bridge of the nose; and a face lacking in expression.
Screening and Diagnosis
Tests that may be done to diagnose Menkes syndrome include X rays of the skull and skeleton to look for abnormalities in bone formation and blood tests to measure copper levels. Measurement of plasma catecholamine levels is an efficient method of testing at-risk newborns.
Treatment and Therapy
There is no cure for Menkes syndrome. Early treatment with intravenous copper acetate, oral copper supplements, or injections of copper histidinate may provide temporary benefit. Other treatments may be used to relieve symptoms.
Prevention and Outcomes
There is no known way to prevent Menkes syndrome. Prenatal treatment with copper has been unsuccessful. Individuals who have a family history of this disorder can talk to a genetic counselor when deciding whether to have children.
Bibliography
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Fujisawa, Chie, et al. "Early Clinical Signs and Treatment of Menkes Disease." Molecular Genetics and Metabolism Reports, vol. 31, 2022, doi.org/10.1016/j.ymgmr.2022.100849. Accessed 10 Sept. 2024.
Kaler, S. G., et al. “Neonatal Diagnosis and Treatment of Menkes Disease.” New England Journal of Medicine 358.6 (2008): 605–14. Print.
Kelly, Evelyn B. Encyclopedia of Human Genetics and Disease. Santa Barbara: Greenwood, 2013. Print.
"Menkes Disease." National Institute of Neurological Disorders and Stroke, 19 July 2024, www.ninds.nih.gov/health-information/disorders/menkes-disease. Accessed 10 Sept. 2024.
"Menkes Disease." National Organization for Rare Disorders, 24 Mar. 2020, rarediseases.org/rare-diseases/menkes-disease/#disease-overview-main. Accessed 10 Sept. 2024.
Menkes, John H., and Harvey B. Sarnat, eds. Child Neurology. 7th ed. Philadelphia: Lippincott, 2005. Print.