The type of Ehlers-Danlos syndrome involves vascular and organ rupture due to type III collagen deficiency.
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 22-year-old man comes to his primary care provider's office because of shoulder pain. He states that he always dislocates his shoulder during his company's annual softball game. He also reports easy bruising and stretchy skin. On physical examination, the patient's skin is hyperextensible and smooth velvety with cigarrette-paper like scars. His thumb is passively dorsiflexed to greater than 90 degrees. A clinical diagnosis of Ehlers-Danlos syndrome is made. A defect in which of the following is most associated with his form of Ehlers-Danlos syndrome?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Miguel Quintana, MD
Ehlers-Danlos syndrome is a group of related genetic conditions which are all caused by defective collagen synthesis.
Normally, collagen provides strength and elasticity to our bodies, and its found in the skin, ligaments, tendons, and bones.
In Ehlers-Danlos syndrome, defective collagen leads to stretchy skin, easy bruising, and joints that are super flexible.
Now, the cells that produce collagen are fibroblasts, and they make five types of collagen.
These five types have specific parts of the body they call home.
Type I collagen makes its home in the skin, tendons, organs, and bones.
Type II collagen makes its home in the cartilage.
Type III collagen, in reticular fibers form a supporting mesh for soft organs like the liver and blood vessels.
Type IV collagen is found in a foundation called the basal lamina, on which the epithelial cells sit.
Finally, there’s type V collagen which is in cell surfaces, hair, and placenta, as well as in places where type I collagen is found.
The synthesis of collagen, like any other protein, starts with the genes.
The name of the genes that encode for a collagen type usually starts with the prefix COL, followed by the collagen number type, and the pro-alpha-chain it encodes.
There are many genes that encode for the different types of collagen, like COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2.
Let’s take the genes COL5A1 and COL5A2 that encode for type V collagen as an example.
In COL5A1, COL stands for collagen.
The five stands for type V collagen and the A1 refers to an alpha-1-chain.
So, COL5A1 encodes a collagen type V alpha-1-chain.
Now, to synthesize type V collagen, for example.
COL5A1 and COL5A2 get transcribed from DNA to mRNA and then gets translated from mRNA to into a string of amino acids that make up a protein.
This process happens many times over.
Now, this string of amino acids consists mostly of glycine and two other random amino acids, usually, proline and lysine that repeat over and over as amino acid triplets.
Ultimately, this peptide forms what is called preprocollagen which can be a collagen type V alpha-1-chain or a collagen type V alpha-2-chain depending on the gene that encodes the protein.
Next, preprocollagen undergoes hydroxylation which is where two enzymes called prolyl hydroxylase and lysyl hydroxylase, with the help of many cofactors like vitamin C, add hydroxyl groups OH− onto proline and lysine.
Then there’s a process called glycosylation, which is done by two enzymes, galactosyl, and glucosyltransferase which add glucose or galactose monomers onto the hydroxyl groups.
After that, three of these chains twist into a triple helix called procollagen.
Now, two combinations can make up the helix or procollagen for type V collagen, three type V alpha-1-chains or two type V alpha-1-chains and one type V alpha-2-chain.