Organic acidemia
Encyclopedia
Organic acidemia, also called organic aciduria, is a term used to classify a group of metabolic disorders
which disrupt normal amino acid metabolism, particularly branched-chain amino acids
, causing a buildup of acids which are usually not present.
The branched-chain amino acids include isoleucine
, leucine
and valine
. Organic acid
s refer to the amino acid
s and certain odd-chained fatty acid
s which are affected by these disorders.
The four main types of organic acidemia are: methylmalonic acidemia
, propionic acidemia
, isovaleric acidemia
, and maple syrup urine disease
.
s. The diagnosis is usually made by detecting an abnormal pattern of organic acids
in a urine sample by gas chromatography-mass spectrometry
. In some conditions, the urine is always abnormal, in others the characteristic substances are only present intermittently. Many of the organic acidemias are detectable by newborn screening
with tandem mass spectrometry.
These disorders vary in their prognosis
, from manageable to fatal, and usually affect more than one organ
system, especially the central nervous system
.
Neurological damage and developmental delay are common factors in diagnosis, with associated symptoms ranging from poor feeding to slow growth
, lethargy, vomiting,
dehydration
, malnutrition
, hypoglycemia
, hypotonia
, metabolic acidosis
, ketoacidosis
, hyperammonemia
, and if left untreated, death
.
gene
s for various enzyme
s important to amino acid metabolism
. Neurological and physiological harm is caused by this impaired ability to synthesize a key enzyme required to break down a specific amino acid, or group of amino acids, resulting in acidemia and toxicity to specific organs systems. Most are inherited as autosomal recessive diseases.
/high carbohydrate
diet, intravenous fluids, amino acid substitution, vitamin supplementation, carnitine, induced anabolism
, and in some cases, tube-feeding.
Inborn error of metabolism
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...
which disrupt normal amino acid metabolism, particularly branched-chain amino acids
Branched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
, causing a buildup of acids which are usually not present.
The branched-chain amino acids include isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
, leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
and valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
. Organic acid
Organic acid
An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are relatively stronger acids. The relative stability of the conjugate...
s refer to the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s and certain odd-chained fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s which are affected by these disorders.
The four main types of organic acidemia are: methylmalonic acidemia
Methylmalonic acidemia
Methylmalonic acidemia , also called methylmalonic aciduria, is an autosomal recessive metabolic disorder. It is a classical type of organic acidemia....
, propionic acidemia
Propionic acidemia
Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia....
, isovaleric acidemia
Isovaleric acidemia
Isovaleric acidemia, also called isovaleric aciduria or isovaleric acid CoA dehydrogenase deficiency, is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine...
, and maple syrup urine disease
Maple syrup urine disease
Maple syrup urine disease , also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia...
.
Diagnosis and Symptoms
Organic acidemias are usually diagnosed in infancy, characterized by urinary excretion of abnormal amounts or types of organic acidOrganic acid
An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are relatively stronger acids. The relative stability of the conjugate...
s. The diagnosis is usually made by detecting an abnormal pattern of organic acids
Urine organic acids
Urine organic acids is a medical diagnostic test used to exclude the possibility that a person has an inborn error of metabolism, usually one of the organic acidemias. The usual method of analysis is tandem mass spectrometry. In most cases a random specimen of as little as 1-5 ml is enough for...
in a urine sample by gas chromatography-mass spectrometry
Gas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...
. In some conditions, the urine is always abnormal, in others the characteristic substances are only present intermittently. Many of the organic acidemias are detectable by newborn screening
Newborn screening
Newborn screening is the process by which infants are screened shortly after birth for a list of disorders that are treatable, but difficult or impossible to detect clinically. Screening programs are often run by state or national governing bodies with the goal of screening all infants born in the...
with tandem mass spectrometry.
These disorders vary in their prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
, from manageable to fatal, and usually affect more than one organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
system, especially the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
Neurological damage and developmental delay are common factors in diagnosis, with associated symptoms ranging from poor feeding to slow growth
Human development (biology)
Human development is the process of growing to maturity. In biological terms, this entails growth from a one-celled zygote to an adult human being.- Biological development:...
, lethargy, vomiting,
dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, metabolic acidosis
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
, ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....
, hyperammonemia
Hyperammonemia
Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary....
, and if left untreated, death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.
Cause
Most of the organic acidemias result from defective autosomalAutosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s for various enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s important to amino acid metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. Neurological and physiological harm is caused by this impaired ability to synthesize a key enzyme required to break down a specific amino acid, or group of amino acids, resulting in acidemia and toxicity to specific organs systems. Most are inherited as autosomal recessive diseases.
Treatment
Treatment or management of organic acidemias vary. There are no effective treatments for all of the conditions, though treatment for some may include a limited proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
/high carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
diet, intravenous fluids, amino acid substitution, vitamin supplementation, carnitine, induced anabolism
Anabolism
Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite...
, and in some cases, tube-feeding.