Inborn errors glycolipid disorders

Question 1

Storage diseases are typically due to what? but luckily …?

Answer 1

Typically due to a missing/malfxning enzyme

• but the accumulating substrate is NOT acutely toxic
• patho is due to gradual accumulation –> cellular dysfxn and death

*DISEASE GETS WORSE OVER TIME

Question 2

Picture in your head, charts of how these diseases look:
Storage disease
Organic acidemias
Mitochondrial diseases

Answer 2

Storage diseases
- progressive build up of substrate

Organic acidemias
- acute periods of worsening with resolution

Mito:
Gradual decline in power

Question 3

Most lysosomal storage diseases are through what mode of inheritance?
Exceptions?
Theme?

Answer 3

Autosomal recessive

exceptions:
Fabry (XLD)
Hunter (XLR)

Common theme:
gradual, progressive, accumulation of lysosomal substrates (usually in lysosome)

Question 4

Population you should note for Gaucher disease

Answer 4

Ashkenazi Jews!

Question 5

Cherry red spots

Answer 5

Tay sachs

Question 6

Acroparesthesias + angiokeratomas

Answer 6

Fabrys

Question 7

Blindness (will die)

Answer 7

Tay sachs

Question 8

Renal failure + proteinuria

Answer 8

Fabry

Question 9

Tx for:
Gaucher
Fabry
Pompe
Hunter

Answer 9

MPS II

Question 10

Crumpled tissue paper in cytoplasm

Answer 10

Gaucher
- lysosomes filled with glucocerebroside
- foamy macrophases
(filled with glucosylceramides)

Question 11

Clinical manifestations that point to storage disease

Answer 11

Coarse facial features
Macroglossia
Short stature

Question 12

Key features of Gaucher Type I

LSD

Answer 12

1. Beta glucosidase aka glucocerebrosidase deficiency
   (glucoceramide lipid accumulates in bone marrow, spleen, liver)
2. Adult
3. Big liver/spleen
4. Anemia/low platelets
5. Ashkenazi jews
6. Erlenmeyer flask deformity

Question 13

Tay sachs Type I key features

LSD

Answer 13

1. Beta hexosaminidase A deficiency
   (GM2 gangliosidosis)
2. Infantile
3. Cherry red spot –> blindness
4. Increased startle reflex
5. Normal liver/spleen
6. seizure
7. mental + motor deterioration

*mainly CNS - Will die

Question 14

Fabry key features

LSD

Answer 14

1. XLinked (females have delayed disease)
2. Alpha Galactosidase deficiency
3. Angiokeratomas
   (bathing trunk distribution)
4. Renal failure
5. Acroparesthesias
6. NORMAL IQ

Question 15

presentation:

Adult male with angiokeratomas + acroparathesias + fam hx of renal failure in males

Answer 15

Fabry

Question 16

Mucopolysaccaridoses are inherited storage diseases caused by:

Answer 16

Defects in the degradation of proteoglycans

breaking down glycosphingolipids

Question 17

13 month old child who died at home had been suffering from CARDIOMEGALY and PROGRESSIVE MUSCLE WEAKNESS for the past 5 months. Prior to death, his EKG showed RAPID CONDUCTION TIME and WIDE AMPLITUDE WRS COMPLEX. A skeletal muscle bx showed ELEVATED GLYCOGEN.

Answer 17

Pompe disease

• kids born nl, presents later
• alpha glucosidase deficiency

Question 18

18 yr old man complains of multi year hx of recurrent painful episodes involving palms and soles of his feet. He also has a hx of irritable bowel synd. and has been hospitalized twice for heat intolerance this past summer. Past med hx sig. for 2 clavicular fractures, myopia, and one hospitalization for pneumonia.

• Name disease and enz affected

Answer 18

Fabry

• alpha galactosidase def.
• low levels of activity in leukocytes

Question 19

Hunter vs Hurler: which one is:
X linked
Has NO corneal clouding
Girl
Alpha iduronidase deficient
Iduronate sulfatase deficient
Tx with Iaronidase
Tx with Idursulfase

Answer 19

X linked
- Hunter (mamas boy)

Has NO corneal clouding
- Hunter

Girl
- Hurler (men are hunters)

Alpha iduronidase deficient
- Hurler

Tx with Iaronidase
- Hurluer (alpha - lAron)

Iduronate sulfatase deficient
- Hunter

Tx with Idursulfase
- Hunter