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Collagen I
- Found in skin and bone
- Important for late-wound repair
- In other words, after skin injury, the initial pink, granulation tissue has ↑ type III collagen and ↓ type I, but as the skin ↑ in strength and heals, the type III collagen is replaced by type I collagen. Therefore, type I collagen has ↑ strength.
- Osteoid (unmineralized bone) secreted by osteoblasts is primarily type I collagen
- The USMLE occasionally tests that type I is found in dentin and cornea.
Osteogenesis imperfecta (OI; “brittle bone disease”)
- Usually caused by deficiency of type I collagen (COL1A# genes).
- Inheritance varies depending on type of OI, but is usually AD.
- There are 17+ types of OI, with many different genes involved.
- USMLE likes defective hydrogen bonding as an answer for OI.
Highest yield features
Blue sclerae
- Most of the time vignettes won’t mention blue sclerae because it’s too easy / buzzwordy, even though it’s the highest yield feature.
Conductive hearing loss
- Conductive hearing loss seen in osteogenesis imperfecta is due to malformation of the middle ear bones (ossicles)
| Child abuse only = avoids eye contact upon being spoken to, spiral fractures, posterior rib fractures, retinal hemorrhages / detachment, subdural hematoma, circular burns, burns that spare flexor creases
Osteogenesis imperfecta = doesn’t respond upon being spoken to, blue sclerae, abnormal dentition |
Fractures at different stages of healing
- Child abuse and osteogenesis imperfecta can both present with multiple fractures in the USMLE question.
| A mother brings her child in with fractures at different stages of healing. The physician notes that the child avoids eye contact when spoken to.
Answer = child abuse, or “contact social services.” On Step1, avoidant behavior = child abuse. A mother brings her child in with fractures at different stages of healing. The physician notes that the child does not respond when spoken to. Answer = osteogenesis imperfecta, or “educate parent about child’s condition.” On Step1, non-response to physician = deafness, not avoidant behavior. |
Genetics point
- With the most common type (typeI OI) due to ↓ production of type I collagen, this is called the null allele effect, where disease occurs because there simply is not enough type I collagen.
- In other words, the normal collagen yielded by the normal gene copy is not affected by the mutant allele.
- This is in contrast to types II and III OI, for instance, which yield an abnormal type I collagen that physically impairs the function of the healthy collagen produced by the normal allele. This is called a dominant-negative effect, and frequently leads to more severe disease and/or miscarriage.
| If the question gives you a classic presentation of a child with multiple fractures and blue sclerae and then asks for the mechanism of disease, the answer is null allele effect (type I).
However, if the question tells you there’s a woman with repeated miscarriages who finally gives birth to a child who demonstrates evidence of fractures in utero, the answer is dominant-negative effect (type II or III). |
Osteopetrosis (Albers–Schönberg disease)
- Fracture disorder in children often mistaken for OI or child abuse
- Characterized by ↑ bone density due to ↓ osteoclast activity
- ↓ osteoclast activity due to deficiency of carbonic anhydrase II inside bone
- Carbonic anhydrase II normally yields an acidic interface via which osteoclasts can resorb bone
- If you subjectively rule out OI and child abuse in a question, think osteopetrosis as the answer.
- Calcium, phosphate, ALP, and PTH level are all normal in osteopetrosis (just as they are in osteoporosis).
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