PATH - Connective Tissue Deficiencies

Question 1

Osteogenesis imperfecta

Answer 1

Genetic bone disorder (brittle bone disease) caused by a variety of gene defects (most commonly *COL1A1 and *COL1A2)

Most common form is *autosomal dominant
with DEC production of otherwise normal *type I
collagen.

SX
-Multiple fractures with minimal trauma
ƒ-Blue sclerae 
ƒ-*Hearing loss (abnormal ossicles)
ƒ-Some forms have tooth abnormalities, including opalescent teeth that wear easily due to lack of dentin (dentinogenesis imperfecta)

Question 2

Ehlers-Danlos syndrome

Answer 2

Faulty *collagen synthesis causing hyperextensible skin, tendency to bleed (easy
bruising), and hyper mobile joints

Can be autosomal dominant or recessive

May be associated with joint dislocation, berry and aortic aneurysms, organ rupture.

• Hypermobility type (joint instability): most common type.
• Classical type (joint and skin symptoms): caused by a mutation in *type V collagen.
• Vascular type (vascular and organ rupture): deficient *type III collagen.

Question 3

Menkes disease

Answer 3

X-linked recessive

connective tissue disease caused by impaired *copper absorption and transport
due to defective *Menkes protein (ATP7A)

Leads to DEC activity of *lysyl oxidase (copper is a
necessary cofactor).

Results in brittle, “kinky” hair, growth retardation, and hypotonia.

Question 4

Elastin

Answer 4

Stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords,
ligamenta flava (connect vertebrae–>relaxed
and stretched conformations).

Rich in nonhydroxylated *proline, *glycine, and *lysine residues

*Tropoelastin with *fibrillin scaffolding.

Broken down by *elastase, which is normally
inhibited by α1-antitrypsin

Wrinkles of aging are due to DEC collagen and elastin production.

Question 5

Marfan syndrome

Answer 5

caused by a defect in

*fibrillin, a glycoprotein that forms a sheath around elastin.

Question 6

Emphysema

Answer 6

can be caused by *α1-antitrypsin deficiency, resulting in excess elastase activity.