Diseases & Conditions


Amino Acid Metabolism

Amino acids are the building blocks of proteins and have many functions in the body. Hereditary disorders of amino acid processing can be the result of defects either in the breakdown of amino acids or in the body's ability to get the amino acids into cells. Because these disorders produce symptoms early in life, newborns are routinely screened for several common ones. In the United States, newborns are commonly screened for phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia, and a number of other inherited disorders, although screening varies from state to state.


Phenylketonuria (PKU) is a disorder that causes a buildup of the amino acid phenylalanine, which is an essential amino acid that cannot be synthesized in the body but is present in food. Excess phenylalanine is normally converted to tyrosine, another amino acid, and eliminated from the body. Without the enzyme that converts it to tyrosine, phenylalanine builds up in the blood and is toxic to the brain, causing mental retardation.

PKU occurs in most ethnic groups. If PKU runs in the family and DNA is available from an affected family member, amniocentesis or chorionic villus sampling with DNA analysis can be performed to determine whether a fetus has the disorder.

Most affected newborns are detected during routine screening tests. Newborns with PKU rarely have symptoms right away, although sometimes an infant is sleepy or eats poorly. If not treated, affected infants progressively develop mental retardation over the first few years of life, which eventually becomes severe. Other symptoms include seizures, nausea and vomiting, an eczema-like rash, lighter skin and hair than their family members, aggressive or self-injurious behavior, hyperactivity, and sometimes psychiatric symptoms. Untreated children often give off a "mousy" body and urine odor as a result of a by-product of phenylalanine (phenylacetic acid) in their urine and sweat.

To prevent mental retardation, phenylalanine intake must be restricted (but not eliminated altogether as people need some phenylalanine to live) beginning in the first few weeks of life. Because all natural sources of protein contain too much phenylalanine for children with PKU, affected children cannot have meat, milk, or other common foods that contain protein. Instead, they must eat a variety of phenylalanine-free processed foods, which are specially manufactured. Low-protein natural foods, such as fruits, vegetables, and restricted amounts of certain grain cereals, can be eaten.

A restricted diet, if started early and maintained well, allows for normal development. However, if very strict control of the diet is not maintained, affected children may begin to have difficulties in school. Dietary restrictions started after 2 to 3 years of age may control extreme hyperactivity and seizures and raise the child's eventual IQ but do not reverse mental retardation. Recent evidence suggests that functioning of some mentally retarded adults with PKU (born before newborn screening tests were available) may improve when they follow the PKU diet.

A phenylalanine-restricted diet should continue for life or intelligence may decrease and neurologic and psychiatric problems may ensue.

Maple Syrup Urine Disease

Children with maple syrup urine disease are unable to metabolize certain amino acids. By-products of these amino acids build up, causing neurologic changes, including seizures and mental retardation. These by-products also cause body fluids, such as urine and sweat, to smell like maple syrup. This disease is most common among Mennonite families.

There are many forms of maple syrup urine disease; symptoms vary in severity. In the most severe form, infants develop neurologic abnormalities, including seizures and coma, during the first week of life and can die within days to weeks. In the milder forms, children initially appear normal but develop vomiting, staggering, confusion, coma, and the odor of maple syrup particularly during physical stress, such as infection or surgery.

In some states, newborns are routinely screened for this disease with a blood test.

Infants with severe disease are treated with dialysis (see Sleep Apnea ). Some children with mild disease benefit from injections of the vitamin B 1 (thiamin). After the disease has been brought under control, children must always consume a special artificial diet that is low in the particular amino acids that are affected by the missing enzyme.


Children with homocystinuria are unable to metabolize the amino acid homocysteine, which, along with certain toxic by-products, builds up to cause a variety of symptoms. Symptoms may be mild or severe, depending on the particular enzyme defect.

Infants with this disorder are normal at birth. The first symptoms, including dislocation of the lens of the eye, causing severely decreased vision, usually begin after 3 years of age. Most children have skeletal abnormalities, including osteoporosis; the child is usually tall and thin with a curved spine, elongated limbs, and long, spiderlike fingers. Psychiatric and behavioral disorders and mental retardation are common. Homocystinuria makes the blood more likely to spontaneously clot, resulting in strokes, high blood pressure, and many other serious problems.

In a few states, children are screened for homocystinuria at birth with a blood test. The diagnosis is confirmed by a test measuring enzyme function in liver or skin cells.

Some children with homocystinuria improve when given vitamin B 6 (pyridoxine) or vitamin B 12 (cobalamin).


Children with tyrosinemia are unable to completely metabolize the amino acid tyrosine. By-products of this amino acid build up, causing a variety of symptoms. In some states, the disorder is detected on the newborn screening tests.

There are two main types of tyrosinemia: I and II. Type I tyrosinemia is most common in children of French-Canadian or Scandinavian descent. Children with this disorder typically become ill sometime within the first year of life with dysfunction of the liver, kidneys, and nerves, resulting in irritability, rickets, or even liver failure and death. Restriction of tyrosine in the diet is of little help. An experimental drug, which blocks production of toxic metabolites, may help children with type I tyrosinemia. Often, children with type I tyrosinemia require a liver transplant.

Type II tyrosinemia is less common. Affected children sometimes have mental retardation and frequently develop sores on the skin and eyes. Unlike type I tyrosinemia, restriction of tyrosine in the diet can prevent problems from developing.

Last full review/revision February 2003

Source: The Merck Manual Home Edition