Branched-chain amino acid metabolism disorders occur when amino acids such as leucine, isoleucine, and valine are not properly broken down (metabolized). They and their toxic by-products build up in the blood and urine, causing various symptoms. These disorders occur when parents pass on to their children the defective genes that cause these disorders.
Amino acids are the building blocks of proteins and have many functions in the body. The body makes some of the amino acids it needs and gets others from food.
Children with a branched-chain amino acid metabolism disorder are unable to completely break down (metabolize) amino acids such as leucine, isoleucine, and valine. The branched-chain amino acids are called “branched-chain” because of their chemical structure.
There are different types of inherited disorders. In branched-chain amino acid metabolism disorders, both parents of the affected child carry 1 copy of the abnormal gene. Because usually 2 copies of the abnormal (recessive) gene are necessary for the disorder to occur, usually neither parent has the disorder. (See also Overview of Hereditary Metabolic Disorders.)
In most states in the United States, these disorders are detected at birth as part of routine newborn screening tests.
Isovaleric acidemia, maple syrup urine disease, methylmalonic acidemia, and propionic acidemia are a few of the many disorders of amino acid metabolism.
Isovaleric asidemia
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 2 forms of isovaleric acidemia. One form begins during the first few days of life. Symptoms that occur in this form 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. The other form begins several months or years after birth. Symptoms in this form come and go and are similar to the symptoms of the form that begins 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 (1 syringe at a time) and replace it with equal volumes of fresh donor blood (called an 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.
Ugonjwa wa Mkojo wa Shira ya Maple
Children with maple syrup urine disease are unable to metabolize the amino acids 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 mild forms, children initially appear normal, but when stressed, such as by an infection, surgery, or other physical stress, they can develop vomiting, staggering when walking, confusion, and coma.
To diagnose maple syrup urine disease, doctors look for elevated levels of amino acids in the blood. The diagnosis is confirmed by genetic testing.
Doctors treat infants with the severe form of the 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 forms of the disease benefit from vitamin B1 (thiamin) supplementation. After the disease is 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.
Asidemia ya Methilimaloni
When an enzyme (a type of protein) called methylmalonyl CoA mutase is not functional, harmful levels of methylmalonic acid build up in the body. This enzyme is needed to break down certain amino acids such as isoleucine and valine as well as some other substances. Methylmalonic acidemia 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.
Asidemia ya Propioniki
When an enzyme (a type of protein) called propionyl CoA carboxylase is not functional, harmful levels of propionic acid build up in the body. This enzyme is needed to break down certain amino acids such as isoleucine and valine as well as some other substances.
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 blood and urine tests 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 infant's 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).
Maelezo Zaidi
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
National Organization for Rare Disorders (NORD): This resource provides information to parents and families about rare diseases, including a list of rare diseases, support groups, and clinical trial resources.
Genetic and Rare Diseases Information Center (GARD): This resource provides and easy to understand information about rare or genetic diseases.
