What is the Difference Between Glutaric Acidemia Type 1 and 2

The key difference between glutaric acidemia type 1 and 2 is that glutaric acidemia type I is an autosomal recessive disorder caused due to the deficiency of glutaryl-CoA dehydrogenase, while glutaric acidemia type II is an autosomal recessive disorder caused due to the deficiency of electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase.

Glutaric acidemia is a genetic disease that is due to the defective metabolism of proteins and fatty acids and the excessive accumulation of their intermediates in the blood and urine. It is an autosomal recessive genetic disorder due to a lack of certain important enzymes. It is mainly of two types; they are glutaric acidemia type 1 and 2.

CONTENTS

1. Overview and Key Difference
2. What is Glutaric Acidemia Type 1
3. What is Glutaric Acidemia Type 2
4. Similarities –  Glutaric Acidemia Type 1 and 2
5. Glutaric Acidemia Type 1 vs 2 in Tabular Form
6. Summary – Glutaric Acidemia Type 1 vs 2

What is Glutaric Acidemia Type 1?

Glutaric acidemia type I is an autosomal recessive genetic disorder in which the body is unable to process certain proteins properly. This disorder is also known as an organic acid disorder. Glutaric acidemia type I is due to mutations in a gene called the GCDH gene. The GCDH gene provides instructions for making an enzyme known as glutaryl-CoA dehydrogenase. This enzyme is normally involved in processing amino acids such as lysine, hydroxylysine, and tryptophan. Due to the deficiency of this enzyme, lysine, hydroxylysine, and tryptophan and their intermediate breakdown products build up in abnormal levels in the blood. This ultimately leads to brain damage, particularly damage to the basal ganglia. The symptoms of this condition may include macrocephaly, subdural haematoma, retinal haemorrhage, poor feeding, loss of appetite, lack of energy, abnormal movements, vomiting, irritability, breathing difficulties, infections, or illnesses.

Moreover, glutaric acidemia type I can be diagnosed through physical examination, blood tests, urine tests, and genetic tests. Furthermore, treatment options for glutaric acidemia type I may include dietary restrictions (limiting high amounts of protein) and a medication called L-carnitine that clears glutaric acid from the body.

What is Glutaric Acidemia Type 2?

Glutaric acidemia type II is an autosomal recessive inherited disorder. It interferes with the ability of the body to process or break down certain proteins and fats. Therefore, incompletely processed proteins and fats can build up in the blood, causing the blood and tissues to become too acidic.

Mutations in three genes called ETFA, ETFB, and ETFDH, can result in this disorder. ETFA and ETFB genes provide instructions for producing an enzyme called electron transfer flavoprotein. On the other hand, the ETFDH gene provides instructions for making an enzyme called electron transfer flavoprotein dehydrogenase. These enzymes help break down proteins and fats. The deficiency of these enzymes leads to partially breaking down nutrients and hence accumulating them in the cells. This damages the cells and causes signs and symptoms of glutaric acidemia type II.

The signs and symptoms of this condition may include weakness, behavioural changes like poor feeding and decreased activity, vomiting, respiratory distress, low muscle tone, an odour of sweaty feet, hepatomegaly, cardiomyopathy, kidney abnormalities, macrocephaly, high forehead, flat nasal bridge, unusual malformed ears, genital abnormalities, other brain malformations, fluid-filled renal cysts, and unusual facial features. Moreover, glutaric acidemia type II can be diagnosed through physical examination, skin biopsy, blood test, urine test, and molecular genetic test. In addition, glutaric aciduria type II is treated with a high carbohydrate, low protein, and low-fat diet and dietary supplementation with riboflavin, carnitine & other supplements.

What are the Similarities Between Glutaric Acidemia Type 1 and 2?

• Glutaric acidemia type 1 and 2 are the two main types of glutaric acidemia.
• Both conditions may lead to metabolic acidosis.
• Children are affected by both disorders.
• Both conditions are autosomal recessively inherited disorders.
• Both conditions may have similar symptoms, such as macrocephaly, poor feeding, and other brain abnormalities, etc.
• These conditions can be diagnosed through physical examination, blood tests, urine tests, and genetic tests.
• They are mainly treated through dietary restrictions.

What is the Difference Between Glutaric Acidemia Type 1 and 2?

A deficiency of glutaryl-CoA dehydrogenase causes glutaric acidemia type I, while a deficiency of enzymes electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase causes glutaric acidemia type II. Thus, this is the key difference between glutaric acidemia type 1 and 2. Furthermore, glutaric acidemia type I is due to mutations in a gene called the GCDH gene, while glutaric acidemia type I is due to mutations in three genes called ETFA, ETFB, and ETFDH.

The below infographic presents the differences between glutaric acidemia type 1 and 2 in tabular form for side-by-side comparison.

Summary – Glutaric Acidemia Type 1 vs 2

Glutaric acidemia is an autosomal recessive genetic disorder mainly present in children. This disorder is due to a lack of certain enzymes that make the body unable to process proteins and fatty acids. The two types of glutaric acidemia are glutaric acidemia type 1 and 2. Glutaric acidemia type I is a result of glutaryl-CoA dehydrogenase deficiency, while glutaric acidemia type II is a result of deficiency of electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase deficiency. So, this summarizes the difference between glutaric acidemia type 1 and 2.

Reference:

1. “Glutaric Acidemia Type 1 – Genereviews®.” – NCBI Bookshelf.
2. “Glutaric Acidemia Type II – about the Disease.” Genetic and Rare Diseases Information Center.

Image Courtesy:

1. “Campomelic dysplasia” By Anna E. von BohlenJohann BöhmRamona PopDiana S. JohnsonJohn TolmieRalf StückerDeborah Morris‐RosendahlGerd Scherer – (CC BY-SA 4.0) via Commons Wikimedia
2. “Image from page 757 of “The diseases of infancy and childhood: designed for the use of students and practitioners of medicine” (1918)” By Internet Archive Book Image (Public Domain) via Flickr