Overview of Amino Acid Metabolism Disorders

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 Acidosis Acidosis is caused by an overproduction of acid that builds up in the blood or an excessive loss of bicarbonate from the blood (metabolic acidosis) or by a buildup of carbon dioxide in the blood... read more ), low blood sugar (hypoglycemia Hypoglycemia Hypoglycemia is abnormally low levels of sugar (glucose) in the blood. Hypoglycemia is most often caused by medications taken to control diabetes. Much less common causes of hypoglycemia include... read more ), 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 Peritoneal dialysis Dialysis is an artificial process for removing waste products and excess fluids from the body, a process that is needed when the kidneys are not functioning properly. There are a number of reasons... read more ). 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.

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 Intellectual Disability Intellectual disability is significantly below average intellectual functioning present from birth or early infancy, causing limitations in the ability to conduct normal activities of daily... read more . 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 Newborn Screening Tests Many serious disorders that are not apparent at birth can nonetheless be detected by various screening tests. Early diagnosis and prompt treatment can reduce or prevent many disorders that may... read more 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 Genetic Screening Before Pregnancy Genetic screening is used to determine whether a couple is at increased risk of having a baby with a hereditary genetic disorder. Hereditary genetic disorders are disorders of chromosomes or... read more .

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 Dialysis ) or by using a machine outside the body to remove and purify blood from the body (called hemodialysis Hemodialysis Dialysis is an artificial process for removing waste products and excess fluids from the body, a process that is needed when the kidneys are not functioning properly. There are a number of reasons... read more ). Doctors also give hydration and nutrition by vein.

Some children with mild disease benefit from injections of vitamin B1 (thiamin Thiamin Deficiency Thiamin deficiency (causing beriberi and other problems) is most common among people whose diet mainly consists of white rice or highly processed carbohydrates in countries with high rates of... read more ). 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 Liver Transplantation Liver transplantation is the surgical removal of a healthy liver or sometimes a part of a liver from a living person and then its transfer into a person whose liver no longer functions. (See... read more cures this disease.

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 Vitamin B12 Deficiency Vitamin B12 deficiency can occur in vegans who do not take supplements or as a result of an absorption disorder. Anemia develops, causing paleness, weakness, fatigue, and, if severe, shortness... read more (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.

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 Acidosis Acidosis is caused by an overproduction of acid that builds up in the blood or an excessive loss of bicarbonate from the blood (metabolic acidosis) or by a buildup of carbon dioxide in the blood... read more ), low blood sugar (hypoglycemia Hypoglycemia Hypoglycemia is abnormally low levels of sugar (glucose) in the blood. Hypoglycemia is most often caused by medications taken to control diabetes. Much less common causes of hypoglycemia include... read more ), 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 Intellectual Disability Intellectual disability is significantly below average intellectual functioning present from birth or early infancy, causing limitations in the ability to conduct normal activities of daily... read more , 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 Peritoneal dialysis Dialysis is an artificial process for removing waste products and excess fluids from the body, a process that is needed when the kidneys are not functioning properly. There are a number of reasons... read more ) or use a machine outside the body to remove and purify blood from the body (called hemodialysis Hemodialysis Dialysis is an artificial process for removing waste products and excess fluids from the body, a process that is needed when the kidneys are not functioning properly. There are a number of reasons... read more ). 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).