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Overview of Amino Acid Metabolism Disorders

By

Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
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Amino acid metabolism disorders are hereditary metabolic disorders. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children. In most hereditary metabolic disorders, both parents of the affected child carry a copy of the abnormal gene. Because usually two copies of the abnormal gene are necessary for the disorder to occur, usually neither parent has the disorder. Some hereditary metabolic disorders are X-linked, which means only one copy of the abnormal gene can cause the disorder in boys.

Amino acids are the building blocks of proteins and have many functions in the body. Hereditary disorders of amino acid processing (metabolism) can result from defects either in the breakdown of amino acids or in the body’s ability to get amino acids into cells. Because these disorders cause symptoms early in life, newborns are routinely screened for several common amino acid disorders. In the United States, newborns are commonly screened for

Newborns also are screened for a number of other inherited disorders, but screening varies from state to state.

Branched-Chain Amino Acids

The branched-chain amino acids are called “branched-chain” because of their chemical structure. Leucine, isoleucine, and valine are the branched-chain amino acids that are the building blocks of proteins in the body. If these amino acids are not properly metabolized, they and their toxic by-products build up in the blood and urine, causing certain disorders.

Isovaleric acidemia

When the amino acid leucine is not properly metabolized, harmful levels of isovaleric acid build up in the body. In isovaleric acidemia, the enzyme needed to break down leucine, called isovaleryl CoA dehydrogenase, is not present or not working correctly. Isovaleric acidemia is also known as sweaty feet syndrome, because accumulated isovaleric acid gives off an odor that smells like sweat.

There are two forms of isovaleric acidemia. One form manifests during the first few days of life, and the other form manifests several months or years after birth. Symptoms that occur in the first few days of life include poor feeding, vomiting, and breathing problems as infants develop a buildup of acid in the blood (metabolic acidosis), low blood sugar (hypoglycemia), and an increase in ammonia in the blood (hyperammonemia). Blood cells may not be made in the bone marrow the way they normally are. Symptoms in the form that manifests later in life come and go and are similar to the symptoms of the form that manifests earlier but are less severe.

Doctors diagnose isovaleric acidemia by doing tests of blood and urine to detect elevated levels of isovaleric acid.

To treat isovaleric acidemia, doctors give hydration and nutrition (including high doses of the sugar dextrose) by vein and glycine supplements to help the body get rid of the excess acid. If these measures do not help, doctors may need to remove small amounts of the infant’s blood (one syringe at a time) and replace it with equal volumes of fresh donor blood (called exchange transfusion) and remove substances from the blood via a catheter inserted through the abdominal wall into the abdomen (called peritoneal dialysis). All affected people need to restrict their consumption of leucine and continue to take supplements of glycine and another amino acid called carnitine. The prognosis is excellent with treatment.

Maple syrup urine disease

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

There are many forms of maple syrup urine disease. In the most severe form, infants have vomiting and lethargy and then develop neurologic abnormalities, including seizures and coma, during the first days of life and can die within days to weeks if untreated. In the milder forms, children initially appear normal, but during infection, surgery, or other physical stress, they can develop vomiting, staggering, confusion, and coma.

Since 2007, nearly every state in the United States has required that all newborns be screened for maple syrup urine disease with a blood test. Doctors also look for elevated levels of amino acids in the blood. The diagnosis is confirmed by genetic testing.

Doctors treat infants with severe disease by strictly limiting the diet and sometimes by removing substances from the blood via a catheter inserted through the abdominal wall into the abdomen (called peritoneal dialysis) or by using a machine outside the body to remove and purify blood from the body (called hemodialysis). Doctors also give hydration and nutrition by vein.

Some children with mild disease benefit from injections of vitamin B1 (thiamin). After the disease has been brought under control, children must always consume a special artificial diet that is low in leucine, isoleucine, and valine. Care providers should have an emergency plan in place for how to handle a sudden attack because it may result in a build-up of toxic substances in the blood and low blood sugar (called metabolic crisis). Sudden attacks are most often triggered by common infections.

A liver transplant cures this disease.

Methylmalonic acidemia

When a certain enzyme is not functional, harmful levels of methylmalonic acid build up in the body. This disorder may also be caused by a deficiency of vitamin B12 (cobalamin). The age at which symptoms start, symptoms, and treatment are similar to those of propionic acidemia except that doctors may give supplements of vitamin B12 instead of biotin.

Propionic acidemia

When a specific enzyme (a type of protein) called propionyl CoA carboxylase is not functional, harmful levels of propionic acid build up in the body.

In most affected infants, symptoms begin in the first days or weeks after birth and include poor feeding, vomiting, and breathing problems as the infants develop a buildup of acid in the blood (metabolic acidosis), low blood sugar (hypoglycemia), and an increase in ammonia in the blood (hyperammonemia). Seizures or coma may occur. Stressors, such as fasting, fever, or infection, may trigger an attack. Children who survive this disorder may have kidney problems, intellectual disability, neurologic abnormalities, and heart problems.

Doctors diagnose propionic acidemia by doing tests of blood and urine to detect elevated levels of propionic acid. The diagnosis is confirmed by measuring levels of propionyl CoA carboxylase in white blood cells or other tissue cells and/or by genetic testing.

To treat propionic acidemia, doctors give hydration and nutrition (including high doses of the sugar dextrose) by vein and restrict the infant's consumption of protein. If these measures do not help, doctors may need to remove substances from the blood via a catheter inserted through the abdominal wall into the abdomen (called peritoneal dialysis) or use a machine outside the body to remove and purify blood from the body (called hemodialysis). As children age, they need to continue dietary restrictions and may need to take carnitine supplements. Doctors often give children antibiotics because bacteria in their intestines can cause propionic acid to build up. Care providers should have an emergency plan in place for how to handle a sudden attack because it may result in a build-up of toxic substances in the blood and low blood sugar (called metabolic crisis).

NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
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