Overview
This lecture provides an updated, high-yield summary of lysosomal storage diseases, focusing on enzyme deficiencies, accumulated substrates, clinical findings, and concise mnemonics for exam preparation.
Approach to Lysosomal Storage Diseases
- Each disease features an enzyme deficiency causing substrate accumulation and specific clinical findings.
- Mnemonics are provided to aid quick recall for exams.
Fabry Disease
- Deficiency: Alpha-galactosidase A.
- Accumulation: 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
- Deficiency: Glucocerebrosidase.
- Accumulation: Glucocerebroside.
- Findings: Osteoporosis, most common lysosomal storage disease, gross (avascular necrotic) femoral head, Gaucher (tissue paper cytoplasm) cells.
- Mnemonic: "Oh my gosh, he's such a bro."
Tay-Sachs Disease
- Deficiency: Hexosaminidase A.
- Accumulation: GM2 ganglioside.
- Findings: Cherry-red macula, onion skin lysosomes, no hepatosplenomegaly.
- Mnemonic: "A gang of six small Jews" (hex = six, Ashkenazi Jewish prevalence); hyphenated name signals cherry-red spot.
Niemann-Pick Disease
- Deficiency: Sphingomyelinase.
- Accumulation: Sphingomyelin.
- Findings: Cherry-red macula, foam cells (lipid-laden macrophages), hepatosplenomegaly.
- Mnemonic: "Pick your nose with a big foamy swinger" (big = hepatosplenomegaly, foam = foam cells, swinger = sphingomyelinase).
Krabbe Disease
- Deficiency: Galactocerebrosidase.
- Accumulation: Galactocerebroside.
- Findings: Globoid cells, oligodendrocyte destruction, optic atrophy.
- Mnemonic: "The glob of gooey crab meat is out of this world."
Hurler & Hunter Syndromes
- Deficiency: Hurler—Alpha-L-iduronidase; Hunter—Iduronate-2-sulfatase.
- Accumulation: Dermatan sulfate and heparan sulfate (both).
- Findings: Both—gargoylism, airway obstruction; Hurler—corneal clouding; Hunter—behavioral aggression, no corneal clouding.
- Mnemonic: "X marks the spot for the hunter" (Hunter is X-linked, aggressive, no corneal clouding).
Metachromatic Leukodystrophy
- Deficiency: Arylsulfatase A.
- Accumulation: Cerebroside sulfate.
- Findings: Central and peripheral demyelination, ataxia, dementia, neuropsychiatric symptoms.
- Mnemonic: "Metapod is a real broken Pokémon" (Metapod = metachromatic; 'is a real' = aryl, 'bro' = cerebro, demyelination = shedding).
Key Terms & Definitions
- Enzyme deficiency — the missing or nonfunctional enzyme causing disease.
- Accumulated substrate — the molecule that builds up due to the deficiency.
- Cherry-red macula — red spot on the retina seen in some lysosomal storage diseases.
- Gargoylism — coarse facial features seen in mucopolysaccharidoses.
- Demyelination — loss of myelin sheath from nerves.
Action Items / Next Steps
- Memorize mnemonics and key findings for each lysosomal storage disease.
- Review associated images (e.g., Gaucher cells, globoid cells).
- Prepare for potential test questions contrasting Tay-Sachs vs. Niemann-Pick and Hunter vs. Hurler.