Inborn Errors: Glycolipid Disorders

Question 1

LSDs are usually what pattern of inheritance? Exceptions?

Answer 1

Autosomal recessive

Exceptions:

• Fabry: alpha galactosidase (XLD)
• Hunter: iduronate-2-sulfatase (XLR)
• Danon disease (XLD)

Question 2

Cherry red spot, think…

Answer 2

Tay Sachs

-Can lead to blindness and death

Question 3

Acroparesthesias, angiokeratomas, think…

Answer 3

Fabry

-Can lead to proteinuria, renal failure

Question 4

Treatment available for

Answer 4

Enzyme replacement:

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

Question 5

Erlenmeyer Flask deformity (bone), think…

Answer 5

Gaucher Disease type I

Question 6

Lysosomes

Answer 6

The garbage (or recycling) centers in cells that are acidic, contain ~50 hydrolase
enzymes, that break down macromolecules into smaller components

Question 7

Lysosomal storage disorders

Answer 7

a group of disorders where defects in lysosomal
‘function’ are present and one (or more) biomolecules cannot be properly degraded and/or
processed
-usually due to absence of lysosomal enzyme
-undigested glyco-lipids and extracellular components that would normally be degraded by lysosomal enzymes accumulate in lysosomes as large inclusions.

Question 8

Are LSD accumulations usually toxic?

Answer 8

No, major problem is gradual accumulation that leads to storage and dysfunction
-In general LSDs are PROGRESSIVE diseases (less acute presentation)

Question 9

What does storage look like? Key buzzwords

Answer 9

• macrocephaly, cognitive regression
• corneal clouding, cherry red spot (Tay Sachs)
• macroglossia, sleep apnea
• hepatosplenomegaly
• renal failure, proteinuria (Fabry)
• dysostosis multiplex (vertebral “beaking”, broad bases of metacarpals, phalages; scoliosis), joint stiffness, short stature

Question 10

Proteinuria/renal failure, think…

Answer 10

Fabry

Question 11

Table

Answer 11

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