Cretinism

Definition

The term mineral deficiency means a condition where the concentration of any one of the minerals essential to human health is abnormally low in the body. In some cases, an abnormally low mineral concentration is defined as that which leads to an impairment in a function dependent on the mineral. In other cases, the convention may be to define an abnormally low mineral concentration as a level lower than that found in a specific healthy population.

The mineral nutrients are defined as all the inorganic elements or inorganic molecules that are required for life. As far as human nutrition is concerned, the inorganic nutrients include water, sodium, potassium, chloride, calcium, phosphate, sulfate, magnesium, iron, copper, zinc, manganese, iodine, selenium, and molybdenum. Some of the inorganic nutrients, such as water, do not occur as single atoms, but occur as molecules. Other inorganic nutrients that are molecules include phosphate, sulfate, and selenite. Phosphate contains an atom of phosphorus. Sulfate contains an atom of sulfur. We do not need to eat sulfate, since the body can acquire all the sulfate it needs from protein. Selenium occurs in foods as selenite and selenate.

There is some evidence that other inorganic nutrients, such as chromium and boron, play a part in human health, but their role is not well established. Fluoride has been proven to increase the strength of bones and teeth, but there is little or no reason to believe that is needed for human life.

The mineral content of the body may be measured by testing samples of blood plasma, red blood cells, or urine. In the case of calcium and phosphate deficiency, the diagnosis may also involve taking x rays of the skeleton. In the case of iodine deficiency, the diagnosis may include examining the patient's neck with the eyes and hands. In the case of iron deficiency, the diagnosis may include the performance of a stair-stepping test by the patient. Since all the minerals serve strikingly different functions in the body, the tests for the corresponding deficiency are markedly different from each other.

Description

Laboratory studies with animals have revealed that severe deficiencies in any one of the inorganic nutrients can result in very specific symptoms, and finally in death, due to the failure of functions associated with that nutrient. In humans, deficiency in one nutrient may occur less often than deficiency in several nutrients. A patient suffering from malnutrition is deficient in a variety of nutrients. In the United States, malnutrition is most often found among severe alcoholics. In part, this is because the alcohol consumption may supply half of the energy requirement, resulting in a mineral and vitamin intake of half the expected level. Deficiencies in one nutrient do occur, for example, in human populations living in iodine-poor regions of the world, and in iron deficient persons who lose excess iron by abnormal bleeding.

Inorganic nutrients have a great variety of functions in the body. Water, sodium, and potassium deficiencies are most closely associated with abnormal nerve action and cardiac arrhythmias. Deficiencies in these nutrients tend to result not from a lack of content in the diet, but from excessive losses due to severe diarrhea and other causes. Iodine deficiency is a global public health problem. It occurs in parts of the world with iodine-deficient soils, and results in goiter, which involves a relatively harmless swelling of the neck, and cretinism, a severe birth defect. The only use of iodine in the body is for making thyroid hormone. However, since thyroid hormone has a variety of roles in development of the embryo, iodine deficiency during pregnancy results in a number of birth defects.

Calcium deficiency due to lack of dietary calcium occurs only rarely. However, calcium deficiency due to vitamin D deficiency can be found among certain populations. Vitamin D is required for the efficient absorption of calcium from the diet, and hence vitamin D deficiency in growing infants and children can result in calcium deficiency.

Dietary phosphate deficiency is rare because phosphate is plentiful in plant and animal foods, but also because phosphate is efficiently absorbed from the diet into the body. Iron deficiency causes anemia (lack of red blood cells), which results in tiredness and shortness of breath.

Dietary deficiencies in the remaining inorganic nutrients tend to be rare. Magnesium deficiency is uncommon, but when it occurs it tends to occur in chronic alcoholics, in persons taking diuretic drugs, and in those suffering from severe and prolonged diarrhea. Magnesium deficiency tends to occur with the same conditions that provoke deficiencies in sodium and potassium. Zinc deficiency is rare, but it has been found in impoverished populations in the Middle East, who rely on unleavened whole wheat bread as a major food source. Copper deficiency is also rare, but dramatic and health-threatening changes in copper metabolism occur in two genetic diseases, Wilson's disease and Menkes' disease.

Selenium deficiency may occur in regions of the world where the soils are poor in selenium. Low-selenium soils can produce foods that are also low in selenium. Premature infants may also be at risk for selenium deficiency. Manganese deficiency is very rare. Experimental studies with humans fed a manganese deficient diet have revealed that the deficiency produces a scaly, red rash on the skin of the upper torso. Molybdenum deficiency has probably never occurred, but indirect evidence suggests that if molybdenum deficiency could occur, it would result in mental retardation and death.

Causes & symptoms

Sodium deficiency (hyponatremia) and water deficiency are the most serious and widespread deficiencies in the world. These deficiencies tend to arise from excessive losses from the body, as during prolonged and severe diarrhea or vomiting. Diarrheal diseases are a major world health problem, and are responsible for about a quarter of the 10 million infant deaths that occur each year. Nearly all of these deaths occur in impoverished parts of Africa and Asia, where they result from contamination of the water supply by animal and human feces.

The main concern in treating diarrheal diseases is dehydration, that is, the losses of sodium and water which deplete the fluids of the circulatory system (the heart, veins, arteries, and capillaries). Severe losses of the fluids of the circulatory system result in shock. Shock nearly always occurs when dehydration is severe enough to produce a 10% reduction in body weight. Shock, which is defined as inadequate supply of blood to the various tissues of the body, results in a lack of oxygen to all the cells of the body. Although diarrheal fluids contain a number of electrolytes, the main concern in avoiding shock is the replacement of sodium and water.

Sodium deficiency and potassium deficiency also frequently result during treatment with drugs called diuretics. Diuretics work because they cause loss of sodium from the body. These drugs are used to treat high blood pressure (hypertension), where the resulting decline in blood pressure reduces the risk for cardiovascular disease. However, diuretics can lead to sodium deficiency, resulting in low plasma sodium levels. A side effect of some diuretics is excessive loss of potassium, and low plasma potassium (hypokalemia) may result.

Iodine deficiency tends to occur in regions of the world where the soil is poor in iodine. Where soil used in agriculture is poor in iodine, the foods grown in the soil will also be low in iodine. An iodine intake of 0.10-0.15 mg/day is considered to be nutritionally adequate, while iodine deficiency occurs at below 0.05 mg/day. Goiter, an enlargement of the thyroid gland (located in the neck), results from iodine deficiency. Goiter continues to be a problem in eastern Europe, parts of India and South America, and in Southeast Asia. Goiter has been eradicated in the United States because of the fortification of foods with iodine. Iodine deficiency during pregnancy results in cretinism in the newborn. Cretinism involves mental retardation, a large tongue, and sometimes deafness, muteness, and lameness.

Iron deficiency occurs due to periods of dietary deficiency, rapid growth, and excessive loss of the body's iron. Human milk and cow milk both contains low levels of iron. Infants are at risk for acquiring iron deficiency because their rapid rate of growth needs a corresponding increased supply of dietary iron, for use in making blood and muscles. Human milk is a better source of iron than cow milk, since about half of the iron in human breast milk is absorbed by the infant's digestive tract. In contrast, only 10% of the iron in cow milk is absorbed by the infant. Surveys of lower-income families in the United States have revealed that about 6% of the infants are anemic indicating a deficiency of iron in their diets. Blood loss that occurs with menstruation in women, as well as with a variety of causes of intestinal bleeding is a major cause of iron deficiency. The symptoms of iron deficiency are generally limited to anemia, and the resulting tiredness, weakness, and a reduced ability to perform physical work.

Calcium and phosphate are closely related nutrients. About 99% of the calcium and 85% of the phosphate in the body occur in the skeleton, where they exist as crystals of solid calcium phosphate. Both of these nutrients occur in a great variety of foods. Milk, eggs, and green, leafy vegetables are rich in calcium and phosphate. Whole cow milk, for example, contains about 1.2 g calcium and 0.95 g phosphorus per kg of food. Broccoli contains 1.0 g calcium and 0.67 g phosphorus per kg food. Eggs supply about one third of the calcium and phosphate of the overall population of the United States. Dietary deficiencies in calcium (hypocalcemia) or phosphate are extremely rare throughout the world. Vitamin D deficiency can be found among young infants, the elderly, and others who may be shielded from sunshine for prolonged periods of time. Vitamin D deficiency impairs the absorption of calcium from the diet, and in this way can provoke calcium deficiency even when the diet contains adequate calcium.

Zinc deficiency has been found among peasant populations in rural areas of the Middle East. Unleavened whole wheat bread can account for 75% of the energy intake in these areas. This diet, which does not contain meat, does contain zinc, but it also contains phytic acid at a level of about 3 g/day. The phytic acid, which naturally occurs in wheat, inhibits zinc absorption. The yeast used to leaven bread produces enzymes that inactivate the phytic acid. Unleavened bread does not contain yeast, and therefore, contains intact phytic acid. The symptoms of zinc deficiency include lack of sexual maturation, lack of pubic hair, and small stature. The amount of phytic acid in a typical American diet cannot provoke zinc deficiency.

Zinc deficiency is relatively uncommon in the United States, but it may occur in adults with alcoholism or intestinal malabsorption problems. Low plasma zinc has been found in patients with alcoholic cirrhosis, Crohn's disease, and celiac disease. Experimental studies with humans have shown that the signs of zinc deficiency are detectable after two to five weeks of consumption of the zinc-free diet. The signs include a rash and diarrhea. The rash occurs on the face, groin, hands, and feet. These symptoms can easily be reversed by administering zinc. An emerging concern is that increased calcium intake can interfere with zinc absorption or retention. Hence, there is some interest in the question of whether persons taking calcium to prevent osteoporosis should also take zinc supplements.

Severe alterations in copper metabolism occur in two genetic diseases, Wilson's disease and Menkes' disease. Both of these diseases are rare and occur in about one in 100,000 births. Both diseases involve mutations in copper transport proteins, that is, in special channels that allow the passage of copper ions through cell membranes. Menkes' disease is a genetic disease involving mental retardation and death before the age of three years. The disease also results in steely or kinky hair. The hair is tangled, grayish, and easily broken. Menkes' disease involves a decrease in copper levels in the serum, liver, and brain, and increases in copper in the cells of the intestines and kidney.

Selenium deficiency may occur in premature infants, since this population naturally tends to have low levels of plasma selenium. Full term infants have plasma selenium levels of about 0.001-0.002 mM, while premature infants may have levels about one third this amount. Whether these lower levels result in adverse consequences is not clear. Selenium deficiency occurs in regions of the world containing low-selenium soils. These regions include Keshan Province in China, New Zealand, and Finland. In Keshan Province, a disease (Keshan disease) occurs which results in deterioration of regions of the heart and the development of fibers in these regions. Keshan disease, which may be fatal, is thought to result from a combination of selenium deficiency and a virus.

Diagnosis

The diagnosis of deficiencies in water, sodium, potassium, iron, calcium, and phosphate involve chemical testing of the blood plasma, urine, and red blood cells.

Iodine deficiency can be diagnosed by measuring the concentration of iodine in the urine. A urinary level greater than 0.05 mg iodine per gram creatinine means adequate iodine status. Levels under 0.025 mg iodine/g creatinine indicate a serious risk.

Normal blood serum magnesium levels are 1.2-2.0 mM. Magnesium deficiency results in hypomagnesemia, which is defined as serum magnesium levels below 0.8 mM. Magnesium levels below 0.5 mM provoke a decline in serum calcium levels. Hypomagnesemia can also result in low serum potassium. Some of the symptoms of hypomagnesemia, which include twitching and convulsions, actually result from the hypocalcemia. Other symptoms of hypomagnesemia, such as cardiac arrhythmias, result from the low potassium levels.

There is no reliable test for zinc deficiency. When humans eat diets containing normal levels of zinc (16 mg/day), the level of urinary zinc is about 0.45 mg/day, while humans consuming low-zinc diets (0.3 mg/day) may have urinary levels of about 0.150 mg/day. Plasma zinc levels tend to be maintained during a dietary deficiency in zinc. Plasma and urinary zinc levels can be influenced by a variety of factors, and for this reason cannot provide a clear picture of zinc status.

Selenium deficiency may be diagnosed by measuring the selenium in plasma (70 ng/mL) or red blood cells (90 ng/mL), where the normal values are indicated. There is also some interest in measuring the activity of an enzyme in blood platelets, in order to assess selenium status. This enzyme is glutathione peroxidase. Platelets are small cells of the bloodstream which are used mainly to allow the clotting of blood after an injury.

Treatment

The treatment of deficiencies in sodium, potassium, calcium, phosphate, and iron usually involves intravenous injections of the deficient mineral.

Iodine deficiency can be easily prevented and treated by fortifying foods with iodine. Table salt is fortified with 100 mg potassium iodide per kg sodium chloride. Goiter was once common in the United States in areas from Washington State to the Great Lakes region, but this problem has been eliminated by iodized salt. Public health programs in impoverished countries have involved injections of synthetic oils containing iodine. Goiter is reversible but, cretinism is not.

Magnesium deficiency can be treated with a magnesium rich diet. If magnesium deficiency is due to a prolonged period of depletion, treatment may include injections of magnesium sulfate (2.0 mL of 50% MgSO₄). Where magnesium deficiency is severe enough to provoke convulsions, magnesium needs to be administered by injections or infusions. For infusion, 500 mL of a 1% solution (1 gram/100 mL) of magnesium sulfate is gradually introduced into a vein over the course of about five hours.

Zinc deficiency and copper deficiency are quite rare, but when they are detected or suspected, they can be treated by consuming zinc or copper, on a daily basis, at levels defined by the RDA.

Selenium deficiency in adults can be treated by eating 100 mg selenium per day for a week, where the selenium is supplied as selenomethionine. The incidence of Keshan disease in China has been reduced by supplementing children with 1.0 mg sodium selenite per week.

Prognosis

In iodine deficiency, the prognosis for treating goiter is excellent, however cretinism cannot be reversed. The effects of iron deficiency are not life-threatening and can be easily treated. The prognosis for treating magnesium deficiency is excellent. The symptoms may be relieved promptly or, at most, within two days of starting treatment. In cases of zinc deficiency in Iran and other parts of the Middle East, supplementation of affected young adults with zinc has been found to provoke the growth of pubic hair and enlargement of genitalia to a normal size within a few months.

Prevention

In the healthy population, all mineral deficiencies can be prevented by the consumption of inorganic nutrients at levels defined by the Recommended Dietary Allowances (RDA). Where a balanced diet is not available, government programs for treating individuals, or for fortifying the food supply, may be used. Government sponsored programs for the prevention of iron deficiency and iodine deficiency are widespread throughout the world. Selenium treatment programs have been used in parts of the world where selenium deficiency exists. Attention to potassium status, and to the prevention of potassium deficiency, is an issue mainly in patients taking diuretic drugs. In many cases of mineral deficiency, the deficiency occurs because of disease, and individual medical attention, rather than preventative measures, is used. The prevention of calcium deficiency is generally not an issue or concern, however calcium supplements are widely used with the hope of preventing osteoporosis. The prevention of deficiencies in magnesium, zinc, copper, manganese, or molybdenum are not major health issues in the United States. Ensuring an adequate intake of these minerals, by eating a balanced diet or by taking mineral supplements, is the best way to prevent deficiencies.

Key Terms

Recommended Dietary Allowance

The Recommended Dietary Allowances (RDAs) are quantities of nutrients that are required each day to maintain human health. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences and may be revised every few years. A separate RDA value exists for each nutrient.

Gale Encyclopedia of Medicine. Gale Research, 1999.