The name is given in honor of Professor John H. Menkes from the USA, who in 1962 was the first to describe the disease and its main clinical features (1). One distinctive trait is the peculiar “kinky” or “steely” hair that even today is a key characteristic leading to a correct diagnosis.
The hair changes provided the first clues of a copper disturbance. David Danks from Melbourne in Australia knew that sheep grazing on copper-poor soil were not suitable for wool production because of twisted and easily breakable wool. In 1972 low blood copper levels were reported in several Menkes babies, and many of the symptoms described by Menkes were consistent with copper deficiency (2). They concluded that poor gut absorption of copper was the basic defect. However, though clinically the disease presents as a copper deficiency, the cause of Menkes is more complex.
Investigation of an affected male fetus in 1973 showed low copper levels in the brain and liver, but an accumulation of copper in other tissues including the placenta (3). This led to the identification of good diagnostic markers for Menkes disease which could also be used for prenatal diagnosis, but requires tissue culturing or measuring of copper in placenta. This tissue is usually not spared for investigation after birth and requires invasive procedures during pregnancy. Copper is required in sufficient amounts to load enzymes, especially in the brain, but too high a surplus can also have detrimental effects, such as in the kidneys, where increased copper levels can make kidneys leaky and cause loss of blood proteins.
New enzyme systems have been linked to Menkes disease which explain a number of symptoms usually associated with other inborn errors of metabolism, making a clear clinical diagnosis difficult in infants before the appearance of hair changes. These enzymes must be evaluated systematically in Menkes disease, to establish their role in Menkes disease. One aim of MIa is to establish a new international scoring system and diagnostic protocol to aid medical professionals in making an earlier diagnosis.
References:
Menkes J.H. , Alter, M. , Steigleder, G.K. , Weakley, D.R. , Sung, J.H (1962). A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics, 29, 764-779
Danks, D.M. , Campbell, P.E. , Stevens, B.J. , Mayne, V. , Cartwright, E. (1972). Menkes's kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics, 50(2), 188-201
Horn, N, Damsgaard, E, Tygstrup, I: Der Fetale Kupfertransport beim Menkes' Syndrom (1975). Mschr Kinderheilk 123, 482-483,