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At a glance

It is a genetic disorder of copper metabolism that is usually diagnosed prenatally which subsequently evolves progressively to a degenerative mechanisms involving several organs of the body and especially the brain. It is characterized by seizures, mental retardation, stunted growth, failure to thrive, unstable body temperature, and very unusual color and texture of hair. Caused by defective intestinal copper absorption that results in severe mental retardation, failure to thrive, sparse hair, and osteoporosis.

Synonyms

Menkes Disease; Menkes Syndrome; Steely Hair Syndrome; Copper Transport Disease; Trichopoliodystrophy Syndrome.

History

The disorder was originally described by John Hans Menkes (1928-2008) in 1962. Dr Menkes was a pediatric neurologist and author of fictional novels and plays. He also identified the Maple Syrup Disease.

Incidence

Worldwide the incidence is estimated at 1:100,000 to 250,000 newborns in the general population. However, in Australia the condition occurs in 1:35,000. This medical condition is lethal before the age of three. It is more common in males than females.

Genetic inheritance

The inheritance is caused by an X-linked recessive trait. It is caused by a mutation in the gene encoding Cu2+-transporting ATPase, alpha polypeptide (gene map locus is Xq12-q13).

Pathophysiology

Defective coding for an intracellular copper-transporting protein called MNK, which travels between the Golgi apparatus and the cell membrane, transporting copper to the exterior of the cell. Defective MNK prevents proper intestinal absorption of copper. The resultant free-copper deficiency affects the function of copper-dependent enzymes such as cytochrome oxidase, tyrosinase, and lysyl oxidase, which results in symptoms and signs of disease.

Diagnosis

Should be considered in any male infant with unexplained seizures, hypothermia, and mental retardation. Serum copper and ceruloplasmin concentrations are low. The copper levels are elevated in fibroblasts and the placenta. Carrier status for the abnormal gene usually can be determined by microscopic examination of multiple hairs from scattered scalp sites for pili torti (twisted hair). Prenatal diagnosis is available (DNA probe).

Clinical aspects

Intrauterine growth retardation, which persists after birth. Neurologic deterioration begins approximately 2 months after birth. Focal cerebral and cerebellar degeneration progress rapidly to decerebration, with characteristic hypotonia, spasticity, and partial and generalized seizures. Strabismus, myopia, and poor visual acuity are common findings. Abnormal thermoregulation with resultant hypothermia is common. Microcephaly occurs as a result of gliosis. The hair is sparse, dull, hypopigmented, brittle, and twisted (pili torti). Hypotonus of the facial musculature gives a chubby-cheek appearance. Micrognathia may be present. Typically, the long bones are osteoporotic. Blood vessels (systemic arteries) become long and tortuous with irregular lumens because of abnormal development of the elastic lamina and thickening of the intima. Aneurysms subsequently develop that may lead to subdural, cerebral, and intestinal hemorrhages. ...

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