Glutaric acidemia type 2 is an
autosomal recessive
In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...
metabolic disorder
A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter t ...
that is characterised by defects in the ability of the body to use
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s and
fats for energy. Incompletely processed proteins and fats can build up, leading to a dangerous chemical imbalance called
acidosis
Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma.
The term ''acidemia'' describe ...
.
Genetics
Mutations in the ''
ETFA'', ''
ETFB'', and ''
ETFDH
Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial is an enzyme that in humans is encoded by the ''ETFDH'' gene. This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron ...
''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s cause glutaric acidemia type II. Mutations in these genes result in a deficiency in one of two enzymes that normally work together in the
mitochondria
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
, which are the energy-producing centers of cells. The ETFA and ETFB genes encode two subunits of the enzyme
electron transfer flavoprotein, while the ETFDH gene encodes the enzyme
electron-transferring-flavoprotein dehydrogenase. When one of these enzymes is defective or missing, the mitochondria cannot function normally, partially broken-down proteins and fats accumulate in the cells and damage them; this damage leads to the signs and symptoms of glutaric acidemia type II.
This condition is inherited in an
autosomal recessive
In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...
pattern, which means the defective gene is located on an
autosome
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...
, and two copies of the gene – one from each parent – are needed to inherit the disorder. The parents of an individual with an autosomal recessive disorder are
carriers of one copy of the defective gene, but do not show signs and symptoms of the disorder themselves.
Diagnosis
Glutaric acidemia type 2 often appears in infancy as a sudden metabolic crisis, in which acidosis and low blood sugar (
hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
) cause weakness, behavior changes, and vomiting. There may also be enlargement of the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...
, and a characteristic odor resembling that of sweaty feet. Some infants with glutaric acidemia type 2 have birth defects, including multiple fluid-filled growths in the kidneys (
polycystic kidneys). Glutaric acidemia type 2 is a very rare disorder. Its precise incidence is unknown. It has been reported in several different ethnic groups.
Treatment
It is important for patients with MADD to strictly avoid fasting to prevent
hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
and crises of
metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
;
for this reason, infants and small children should eat frequent meals.
Patients with MADD can experience life-threatening metabolic crises precipitated by common childhood illnesses or other stresses on the body,
so avoidance of such stresses is critical.
Patients may be advised to follow a diet low in fat and protein and high in carbohydrates, particularly in severe cases.
Depending on the subtype,
riboflavin
Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved i ...
(100-400 mg/day),
coenzyme Q10
Coenzyme Q, also known as ubiquinone and marketed as CoQ10, is a coenzyme family that is ubiquitous in animals and most bacteria (hence the name ubiquinone). In humans, the most common form is coenzyme Q10 or ubiquinone-10.
It is a 1,4-benzo ...
(CoQ10),
L-carnitine
Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, an ...
,
or
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
supplements may be used to help restore energy production. Some small, uncontrolled studies
have reported that racemic salts of
beta-hydroxybutyrate
β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxy ...
were helpful in patients with moderately severe disease; further research is needed.
See also
*
Glutaric acidemia type 1
*
Riboflavin-responsive exercise intolerance Riboflavin-responsive exercise intolerance (SLC25A32 deficiency) is a rare disorder caused by mutations of the SLC25A32 gene that encodes the mitochondrial folate transporter. Patients suffer from exercise intolerance and may have disrupted motor f ...
- similar in biochemical features, also responsive to riboflavin
References
''This article incorporates public domain text fro
The U.S. National Library of Medicine'
External links
{{Fatty-acid metabolism disorders
Amino acid metabolism disorders
Autosomal recessive disorders