Glutaric acidemia type II
Glutaric acidemia type II is a rare inherited metabolic disorder that prevents the body from properly breaking down proteins and fats, leading to dangerous acid buildup and life-threatening metabolic crises.
Overview
Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. When these nutrients are incompletely processed, they accumulate in the body and cause the blood and tissues to become dangerously acidic, a condition known as metabolic acidosis.
Symptoms and Clinical Features
The signs and symptoms of glutaric acidemia type II vary widely in severity and can appear at different stages of life.
Metabolic Crisis
In infancy or early childhood, the disorder typically presents as a sudden, life-threatening episode called a metabolic crisis. These crises can be triggered by common childhood illnesses or other physical stresses. Symptoms include:
- Acidosis
- Low blood glucose (hypoglycemia)
- Weakness
- Vomiting
- Behavioral changes, such as poor feeding and decreased activity
Severe Physical Abnormalities
In the most severe cases, affected individuals may be born with physical malformations, which can include:
- Brain malformations
- An enlarged liver (hepatomegaly)
- A weakened and enlarged heart (dilated cardiomyopathy)
- Fluid-filled cysts and other malformations of the kidneys
- Unusual facial features and genital abnormalities
- A characteristic body odor resembling sweaty feet
Mild and Late-Onset Forms
Some individuals experience milder forms of the disorder that begin later in childhood or during adulthood. In the mildest cases, the first sign of the condition may be muscle weakness that develops in adulthood.
Frequency
Glutaric acidemia type II is a very rare disorder. Its precise incidence is unknown, though it has been reported across several different ethnic groups.
Causes & Genetic Factors
Mutations in any of three genes—ETFA, ETFB, or ETFDH—can cause glutaric acidemia type II:
- The ETFA and ETFB genes provide instructions for making the subunits of an enzyme called electron transfer flavoprotein.
- The ETFDH gene provides instructions for making an enzyme called electron transfer flavoprotein dehydrogenase.
Both enzymes are active in the mitochondria, the energy-producing centers of cells, where they help break down proteins and fats. A deficiency in either enzyme causes partially broken down nutrients to accumulate and damage cells. Mutations that result in a complete loss of either enzyme lead to the most severe symptoms, while mutations that allow the enzymes to retain some activity result in milder forms of the disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern. This means both copies of the gene in each cell must have mutations for the individual to be affected. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.