Collagen disorders: Pathology review

A 5 year old male, named Mateo, is brought by his father to the emergency department for right thigh pain. Past medical history reveals multiple fractures following minor traumas. Upon further questioning, Mateo’s father states that Mateo has been experiencing progressive hearing loss. On physical examination, you notice that Mateo’s scleras appear bluish in color. You then decide to order an X-ray, which shows a fracture of the right femur.

Later that day, you see Mary, an 18 year old female, who comes in complaining of left shoulder pain after she tripped during a basketball game. She mentions that she's had multiple joint dislocations since childhood, including two elbow dislocations in the past year. Mary has also noticed that her skin is “stretchy” when pulled, and seems to bruise easily. You then order an X-ray, which reveals anterior dislocation of the left shoulder.

Based on the initial presentation, both Mateo and Mary seem to have some form of a collagen disorder. So let’s first start with a bit of physiology real quick! What’s high yield for your exams is that there are five major types of collagen. Type I collagen is mainly found in the skin, sclera, teeth, bones, tendons, and ligaments. Type II collagen is abundant in cartilage. Type III collagen is mainly present in the walls of blood vessels, as well as hollow organs, like the intestines and the uterus. Type IV collagen is found in the basement membrane of the glomeruli of the kidneys, as well as the lens of the eyes, and cochlea of the inner ears. Finally, there’s type V collagen, which is found in cell surfaces, hair, and placenta, as well as in places where type I collagen is found.

Now, collagen synthesis starts when the collagen genes get transcribed from DNA to mRNA, which gets translated into an alpha chain of amino acids, which mostly consists of repetitive sequences of glycine, proline, and lysine. Some of these proline and lysine residues will then need to get hydroxylated, meaning that hydroxyl groups are added by the enzyme hydroxylase, resulting in the formation of hydroxyproline and hydroxylysine. What’s high yield for your exams is that hydroxylase requires vitamin C, or ascorbic acid, as a cofactor.