Inborn Errors: Glycolipid Disorders Flashcards Preview

DEMS Unit 2 Part 2 > Inborn Errors: Glycolipid Disorders > Flashcards

Flashcards in Inborn Errors: Glycolipid Disorders Deck (19):
1

Key things to focus on from Dr. Taylor's lecture

1. Recognition
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

2

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

3

Treatment strategies for lysosomal storage diseases

1. Substrate inhibition
2. Enzyme replacement therapy
3. Chaperones (help stabilize the native enzyme)

4

Glycolipids

- molecules that contain both carbohydrate and lipid components
- roles in cell signaling, cell membranes, and an energy source

5

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

6

Organic acidemias

Fairly acute problem (House on fire)

vs. Mitochondrial disease (House without power)

vs. Storage disease (House w/o garbage or recycling service)

7

LSD mode of inheritance

- Most are autosomal recessive with the exception of: Fabry XLD, Hunter XLR, Danon disease XLD)

Men like to Hunt (XLR)

8

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

9

LSD incidence

- Rare individually but overall incidence is (1:5000)
- Populations:
- Gaucher: 1:855 in Ashkenazi Jews (also elevated risk of Tay Sachs)
- Aspartylglucosaminuria: 1:18,500 (Finnish)

These are due to founder effects!

10

Unique phenotypes

- Cherry red spot (Tay Sachs)
- Acroparethesias, angiokeratomas (Fabry) (burning palms)

11

Complications

- blindness, will die (Tay Sachs)
- renal failure (fabry)

12

Treatment available

- Gaucher, Fabry, Pompe, Hunter (MPSII), Maroteaux-Lamy (MPS VI)

13

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

14

Classic Gaucher cell in bone marrow

"tissue paper" appearance of cytoplasm caused by enlarged, elongated lysosomes filled with glucocerebroside

15

Cell with alpha-mannosidosis

Lysosomal swelling

16

Cell with Pompe

Intralysosomal storage

17

Dystosis multiplex

1. Vertebral "beaking"
2. Broad bases of metacarpals and phalanges

18

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!

19

Cherry red spot

1. Tay Sachs Disease
2. White pallor surrounding a central red, stuff is accumulating in the nearby ganglion cells

This is an early finding. The white milky fluid will disperse and you can no longer see it as the disease progresses