Flashcards in Inborn Errors: Glycolipid Disorders Deck (19):
Key things to focus on from Dr. Taylor's lecture
2. Key diseases -- specific features/comps and which enzymes are involved so that you can determine which tests to order and what the Rx is
Lysosomal storage diseases
Can't get rid of it, end up storing it...
A little bit like a garbage strike or recycling strike within the cells. Over the course of years, the disease progress
Treatment strategies for lysosomal storage diseases
1. Substrate inhibition
2. Enzyme replacement therapy
3. Chaperones (help stabilize the native enzyme)
- molecules that contain both carbohydrate and lipid components
- roles in cell signaling, cell membranes, and an energy source
Storage diseases pathophysiology
- Substrates normally degraded end up accumulating
- Typically due to a missing/malfunctioning enzyme
- Not acutely toxic, usually gradual accumulation --> cellular dysfunction and death
Lysosomal storage diseases represent important examples of storage diseases
Fairly acute problem (House on fire)
vs. Mitochondrial disease (House without power)
vs. Storage disease (House w/o garbage or recycling service)
LSD mode of inheritance
- Most are autosomal recessive with the exception of: Fabry XLD, Hunter XLR, Danon disease XLD)
Men like to Hunt (XLR)
Pathophys of LSD
swollen lysosome --> swollen cell --> cell dysfunction --> organ dysfunction
All cells are probably affected, but the cells producing or supposedly degrading the problem protein are the most affected.
Usually normal delivery but failed breakdown
- Rare individually but overall incidence is (1:5000)
- Gaucher: 1:855 in Ashkenazi Jews (also elevated risk of Tay Sachs)
- Aspartylglucosaminuria: 1:18,500 (Finnish)
These are due to founder effects!
- Cherry red spot (Tay Sachs)
- Acroparethesias, angiokeratomas (Fabry) (burning palms)
- blindness, will die (Tay Sachs)
- renal failure (fabry)
- Gaucher, Fabry, Pompe, Hunter (MPSII), Maroteaux-Lamy (MPS VI)
What does storage look like?
- Skin: Coarse skin
- Skull: Macrocephaly, cognitive regression
- Eyes: Corneal clouding, cherry red spot
- ENT: Macroglossia, sleep apnea
- Liver: hepatosplenomegaly
- Kidneys: proteinuria (fabry)
- Skeletal: dystosis multiplex, joint stiffness, short stature
Classic Gaucher cell in bone marrow
"tissue paper" appearance of cytoplasm caused by enlarged, elongated lysosomes filled with glucocerebroside
Cell with alpha-mannosidosis
Cell with Pompe
1. Vertebral "beaking"
2. Broad bases of metacarpals and phalanges
Erlenmeyer flask deformity
Marrow infiltration from Gaucher cells displaces normal marrow, causes femur to look like an erlenmeyer flask.
Found in Gaucher Disease Type I
PROBABLY ON THE EXAM!