Excerpt from Menkes Kinky Hair Disease

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Background

Menkes kinky hair syndrome is an X-linked recessive multisystemic lethal disorder of copper metabolism. The clinical phenotype is marked by fine silvery wiry hair, doughy skin, connective tissue disturbances, and progressive neurologic deterioration. In 1962, Menkes et al¹ first described the syndrome, and, 10 years later, Danks et al^{2, 3} noted the association with copper metabolism. The affected copper-transporting p-type ATPase (ATP7A) gene was cloned in 1993.

In Menkes kinky hair syndrome, intestinal copper uptake by brush border cells is normal, but copper transport to other tissues is affected. This change alters the activities of various copper-dependent metalloenzymes. Male infants who are affected typically die by the time they are aged 2-3 years. Carrier female patients may have only a hair-shaft abnormality (ie, pili torti).

Pathophysiology

A defect in intestinal copper transport with associated low serum copper and ceruloplasmin levels results in a deficiency in copper-dependent enzyme activity. Copper-dependent metalloenzymes relevant to the clinical phenotype include tyrosinase (pigmentation of skin and hair), lysyl oxidase (elastin and collagen cross-linking), ascorbate oxidase (skeletal development), monoamine oxidase (possibly responsible for pili torti), superoxide dismutase (free-radical detoxification), dopamine beta-hydroxylase (catecholamine production), peptidyl-glycine alpha-amidating mono-oxygenase (bioactivation of peptide hormones), and cytochrome c oxidase (electron transport and possibly responsible for hypothermia). The resulting defects are reflected in the clinical phenotype.

Frequency

United States

Menkes kinky hair syndrome occurs in 1 case per 300,000 population.

International

In Australia, this condition occurs in 1 case per 35,000 population. Worldwide, it occurs in 1 case per 300,000 population.

Mortality/Morbidity

• Progressive neurologic deterioration occurs.
• Death, usually due to pneumonia, occurs by the time the patient is aged 2 or 3 years.

Race

No racial predilection exists.

Sex

• The phenotype of the syndrome is manifest in male patients.
• Female carriers may have pili torti and uneven skin pigmentation, which appears unilaterally or along the lines of Blaschko.

Age

Symptoms are noted within the patient's first few months of life.

• Hair changes may not be present in newborns, and not all hairs are affected.
• Seizures usually begin within the patient's first few days or months of life.
• Hypotonia and developmental delays are typically noted during the patient's first year of life.

Please click here to view the full topic text: Menkes Kinky Hair Disease