Lysosomal Storage Diseases 2021 Update

Introduction

• Update of original lysosomal storage disease video from four years ago.
• New high-yield information relevant for exams like USMLE or COMLEX.
• Video by Dirty Medicine.

Support and Membership

• Introduced a new Dirty Medicine membership to support the channel.
  • $4.99/month for perks such as a logo next to comments and voting on video topics.

Lysosomal Storage Diseases Overview

• Each disease involves:
  • Enzyme Deficiency
  • Accumulating Substrate
  • Clinical/Histopathological Findings

Fabry Disease

• Enzyme Deficiency: Alpha galactosidase A
• Accumulating Substrate: Ceramide trihexoside
• Findings: Hypohidrosis, angiokeratomas, renal failure, peripheral neuropathy
• Mnemonic: "My favorite activity is making a ceramic galaxy, sorry to keep harping on it."

Gaucher Disease

• Enzyme Deficiency: Glucocerebrosidase
• Accumulating Substrate: Glucocerebroside
• Findings: Osteoporosis, most common lysosomal storage disease, avascular necrotic femoral head, Gaucher cells (tissue paper cytoplasm)
• Mnemonic: "Oh my gosh, he's such a bro."

Tay-Sachs Disease

• Enzyme Deficiency: Hexosaminidase A
• Accumulating Substrate: GM2 ganglioside
• Findings: Cherry red macula, onion-skinned lysosomes, no hepatosplenomegaly
• Mnemonic: "A gang of six small Jews."
  • Tay-Sachs affects Ashkenazi Jews.
  • Hyphenated diseases have cherry red macula.

Niemann-Pick Disease

• Enzyme Deficiency: Sphingomyelinase
• Accumulating Substrate: Sphingomyelin
• Findings: Cherry red macula, foam cells, hepatosplenomegaly
• Mnemonic: "You pick your nose with a big foamy swinger."

Krabbe Disease

• Enzyme Deficiency: Galactocerebrosidase
• Accumulating Substrate: Galactosylceramide
• Findings: Globoid cells, oligodendrocyte destruction, optic atrophy
• Mnemonic: "The glob of gooey crab meat is out of this world."

Hunter and Hurler Syndromes

• Common Accumulating Substrates: Dermatan sulfate, Heparan sulfate

Hunter Syndrome (Blue)

• Enzyme Deficiency: Iduronate-2-sulfatase
• Findings: Behavioral aggression, no corneal clouding
• Mnemonic: "X marks the spot for the hunter."

Hurler Syndrome (Red)

• Enzyme Deficiency: Alpha-L-iduronidase
• Findings: Corneal clouding

Metachromatic Leukodystrophy

• Enzyme Deficiency: Arylsulfatase A
• Accumulating Substrate: Cerebroside sulfate
• Findings: Demyelination (central and peripheral), ataxia, dementia, neuropsychiatric symptoms
• Mnemonic: "Metapod is a real broken Pokémon."
  • Metapod associated with demyelination, ataxia, and dementia.

Conclusion

• Importance of continued support to the channel through memberships.
• Reflections on the growth and future of the channel.