Lysosomal Storage Diseases

Question 1

Gaucher

Answer 1

• AR
• deficient enzyme: beta-glucocerebrosidase
• accumulated: glucocerebroside
• signs/sxs: gaucher cells (macrophages that look like crumpled tissue paper), hepatosplenomegaly, pancytopenia, severe bone and joint pain

Question 2

Hurler

Answer 2

• AR
• deficient enzyme: alpha-L-iduronidase
• accumulated: dermatan and heparan sulfate
• signs/sxs: gargoylism, corneal clouding, hepatosplenomegaly, developmental delay
• “L” in hurLer for alpha-L-iduronidase
• don’t need to see as well if you are hurling something than when hunting for something (corneal clouding, none in Hunter)

Question 3

Hunter

Answer 3

• X-linked (super sexist, but most times I think of men as hunters)
• deficient enzyme: iduronate sulfatase
• accumulated: dermatan and heparan sulfate (same as Hurler)
• signs/sxs: same as Hurler except milder and no corneal clouding
• Hunter needs to see clearly

Question 4

Niemann-Pick

Answer 4

• AR
• deficient enzyme: sphingomyelinase
• accumulated: sphingomyelin
• signs/sxs: hepatosplenomegaly, cherry-red spot in macula, foam cells, progressive neurodegeneration
• “after PICKing out the perfect dress, she was pissed to find out that her delivery box from Niemann-Marcus was just full of foam (cells) :( … she then got so upset that she drank herself into liver failure (hepatosplenomegaly) and then had a seizure”

Question 5

Tay Sachs

Answer 5

• AR
• deficient enzyme: beta-hexosaminidase A (Tay “Sixth” –> hexagon has six sides)
• accumulated: GM2 ganglioside (a poor M2 would never be able to shop at Sachs Fifth Avenue)
• signs/sxs: cherry-red spot in macula, progressive neurodegeneration, no hepatosplenomegaly
• “my girl Tay instead decided to order her dress from Sachs Fifth Avenue and was relieved when there was no foam, but she was so excited that she had a seizure. She didn’t feel the need to drink, though.”

Question 6

Krabbe

Answer 6

• AR
• deficient enzyme: galactocerebrosidase (“did you hear about the Crab they sent to space? It was galactic!”)
• accumulated: galatosylsphingosine and galactocerebroside (such a galactic crab!)
• signs/sxs: progressive neurodegeneration, optic atrophy (“the galactic sun blinded the crab”)

Question 7

Metachromatic Leukodystrophy

Answer 7

• AR
• deficient enzyme: arylsulfatase A
• accumulated: cerebroside sulfate
• signs/sxs: muscle wasting, dementia, ataxia

Question 8

Fabry Disease

Answer 8

• X-linked
• deficiency: alpha-galactosidase
• accumulated: ceramide trihexoside (“I just opened a new store called “Ceramics and Fabrics!”)
• signs/sxs: angiokeratomas (punctuate, dark red, non-blanching macules and papules that classically occur between the umbilicus and the knees), cardiac and renal involvement, painful neuropathy (acroparesthesia: episodic, often debilitating, burning neuropathic pain in the extremities)
• without enzyme replacement therapy, progressive renal insufficiency leading to renal failure and death may occur