Menkes syndrome, also known as "kinky hair" disease, is a rare disorder that occurs in males with a frequency of 1 in 140,000. This X-linked condition is characterized by impaired efflux of dietary copper from intestinal cells into the bloodstream due to a dysfunction in a copper-transporting ATPase called ATP7A. As a result, there is a systemic copper deficiency. This deficiency leads to low levels of unbound copper in both urine and serum, as well as a decrease in the concentration of ceruloplasmin, a protein that carries over 90% of the circulating copper. Menkes syndrome is associated with progressive neurologic degeneration, connective tissue disorders, and noticeable changes in hair. Treatment options include the administration of copper through injection, although its effectiveness varies. It is worth noting that the mildest form of Menkes syndrome is called occipital horn syndrome.

On the other hand, Wilson disease is an autosomal-recessive disorder that affects approximately 1 in 35,000 live births. In this condition, the liver's ability to excrete excess copper is impaired due to a dysfunction in a copper-transporting ATPase called ATP7B. As a result, copper accumulates in the liver, leaks into the bloodstream, and gets deposited in various organs such as the brain, eyes, kidneys, and skin. In contrast to Menkes syndrome, Wilson disease is characterized by high levels of unbound copper in urine and serum. Individuals with Wilson disease experience hepatic dysfunction, as well as neurologic and psychiatric symptoms. A distinctive feature of Wilson disease is the presence of Kayser-Fleischer rings, which are deposits of copper in the cornea. The standard treatment for Wilson disease involves lifelong use of copper-chelating agents, such as penicillamine.

The absorption of minerals, including copper, can be influenced by the presence of other minerals. For instance, an excess of zinc can decrease the absorption of copper. It is important to note that copper is essential for the absorption of iron.

Moving on to iron, the adult body typically contains 3-4 grams of this mineral. Iron is a component of numerous proteins, both catalytic and noncatalytic. It can be bound to sulfur as observed in the Fe-S proteins involved in the electron transport chain, or it can be part of the heme prosthetic group found in proteins like hemoglobin (which constitutes approximately 70% of all iron in the body), myoglobin, and cytochromes. It is crucial to highlight that free ionic iron can be toxic, as it can generate the hydroxyl radical, a reactive oxygen species. Dietary iron is available in two forms: heme iron, which is present in animal sources, and nonheme iron, found in plant sources. Heme iron is less abundant but is better absorbed. Good dietary sources of iron include meat, poultry, certain shellfish, ready-to-eat cereals, lentils, and molasses. Approximately 10% of ingested iron is absorbed by the body, which amounts to around 1-2 milligrams per day. This amount is sufficient to replace the iron lost primarily through cell shedding.
Menkes syndrome: In Menkes syndrome (“kinky hair” disease), a rare X-linked (1:140,000 males) disorder, efflux of dietary Cu out of intestinal enterocytes into the circulation by a Cu-transporting ATPase (ATP7A) is impaired. This results in systemic Cu deficiency. Consequently, urinary and serum free (unbound) Cu are low, as is the concentration of ceruloplasmin, which carries over 90% of the Cu in the circulation (Fig. 29.6). Progressive neurologic degeneration and connective tissue disorders are seen, as are changes to hair. Parenteral administration of Cu has been used as a treatment with varying success. [Note: The mildest form of Menkes syndrome is called occipital horn syndrome.] 2.
Wilson disease: In Wilson disease, an autosomal-recessive (AR) disorder affecting 1:35,000 live births, efflux of excess Cu from the liver by ATP7B is impaired. Cu accumulates in the liver; leaks into the blood; and is deposited in the brain, eyes, kidneys, and skin. In contrast to Menkes syndrome, urinary and serum free Cu are high (see Fig. 29.6). Hepatic dysfunction and neurologic and psychiatric symptoms are seen. Kayser-Fleischer rings (corneal deposits of Cu) may be present (Fig. 29.7). Life-long use of Cu-chelating agents, such as penicillamine, is the treatment.
The bioavailability (percent of the amount ingested that is able to be absorbed) of a mineral can be influenced by other minerals. For example, excess Zn decreases the absorption of Cu, and Cu is needed for the absorption of Fe.
B. Iron
The adult body typically contains 3–4 g of Fe. It is a component of many proteins, both catalytic (for example, hydroxylases such as prolyl hydroxylase, see p. 47) and noncatalytic. Iron can be linked to sulfur (S) as seen in the Fe–S proteins of the electron transport chain (see p. 75), or it can be part of the heme prosthetic group (see p. 25) in proteins such as hemoglobin (~70% of all Fe), myoglobin, and the cytochromes. [Note: Free ionic Fe is toxic because it can cause production of the hydroxyl radical, a reactive oxygen species (ROS).] Dietary Fe is available as Fe2+ in heme (animal sources) and Fe3+ in nonheme sources (plants). Heme iron is less abundant, but it is better absorbed. Meat, poultry, some shellfish, ready-toeat cereals, lentils, and molasses are good dietary sources of Fe. About 10% of ingested Fe is absorbed. This amount, ~1−2 mg/day, is sufficient to replace Fe lost from the body primarily by the sloughing of cells.
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