430.2 ๐Ÿ“š ๅœ‹่€ƒ็‰ˆ๏ผˆ้†ซๅธซๅœ‹่€ƒ / PGY OSCE๏ผ‰

430.2.0.1 ๐Ÿ“Œ Cram Sheet

430.2.0.1.1 ๐Ÿ”ฅ ้ซ˜ yield 15
  1. LSD ๅ…ฑ้€š pattern๏ผšlysosomal enzyme deficiency โ†’ substrate accumulation โ†’ multi-organ
  2. Gaucher disease๏ผšฮฒ-glucosidase (GBA1), type 1 non-CNS, hepatosplenomegaly + thrombocytopenia + bone disease + Erlenmeyer flask
  3. Gaucher tx๏ผšimiglucerase ERT OR eliglustat/miglustat SRT
  4. Gaucher ้ขจ้šช๏ผšParkinson disease๏ผˆๆœ€ๅคง genetic risk for PD๏ผ‰
  5. Fabry๏ผšฮฑ-galactosidase A (GLA), X-linked
  6. Fabry features๏ผšacroparesthesia + angiokeratoma + cornea verticillata + CKD/proteinuria + LVH + stroke
  7. Fabry tx๏ผšagalsidase ฮฑ/ฮฒ ERT OR migalastat chaperone (amenable mutations)
  8. Pompe๏ผšGAA deficiency, lysosomal glycogen
  9. IOPD vs LOPD๏ผšinfantile (cardiac hypertrophy) vs adult (limb-girdle + respiratory)
  10. Pompe tx๏ผšalglucosidase alfa๏ผˆ22E avalglucosidase, cipaglucosidase+miglustat๏ผ‰
  11. MPS I๏ผšฮฑ-L-iduronidase, three subtypes (Hurler/Scheie/H-S), HSCT + laronidase
  12. MPS II Hunter๏ผšX-linked, no corneal clouding, idursulfase
  13. Niemann-Pick A/B๏ผšASM, foam cells, olipudase alfa๏ผˆ22E new๏ผ‰
  14. NPC๏ผšcholesterol transport, VSGP, miglustat
  15. Tay-Sachs๏ผšHexA, cherry-red spot, Ashkenazi
430.2.0.1.2 ๐Ÿ”ข ๅฟ…่ƒŒ ERT ๅˆ—่กจ
็–พ็—… ERT FDA Year
Gaucher imiglucerase, velaglucerase, taliglucerase 1991, 2010, 2012
Fabry agalsidase ฮฑ/ฮฒ, pegunigalsidase 2001, 2003, 2023
Pompe alglucosidase, avalglucosidase, cipaglucosidase+miglustat 2006, 2021, 2023
MPS I laronidase 2003
MPS II idursulfase 2006
MPS IVA elosulfase alfa 2014
MPS VI galsulfase 2005
MPS VII vestronidase alfa 2017
ASMD (NPD B) olipudase alfa 2022
LAL-D sebelipase alfa 2015
CLN2 cerliponase alfa (IT) 2017
430.2.0.1.3 ๐Ÿ”ข ๅฟ…่ƒŒ oral ๅฐๅˆ†ๅญ
็–พ็—… Drug ๆฉŸ่ฝ‰
Gaucher eliglustat (CYP2D6 NM/IM) SRT
Gaucher miglustat SRT
Fabry migalastat (amenable mutations) chaperone
NPC miglustat (off-label) SRT

430.2.0.2 โญ ้ซ˜ yield ๅœ–่กจ

430.2.0.2.1 LSD ไธป่ฆ็–พ็—… quick chart
Disease Enzyme Inheritance Storage Key feature Tx
Gaucher ฮฒ-glucosidase (GBA1) AR glucocerebroside hepatosplenomegaly, thrombocytopenia, bone, Erlenmeyer flask, PD risk ERT, SRT
Fabry ฮฑ-Gal A (GLA) XL Gb3 acroparesthesia, angiokeratoma, cornea verticillata, CKD, LVH, stroke ERT, migalastat
Pompe GAA AR lysosomal glycogen IOPD cardiac / LOPD limb-girdle + respiratory ERT
MPS I (Hurler/Scheie/H-S) ฮฑ-L-iduronidase AR DS + HS coarse facies, organomegaly, corneal clouding HSCT + ERT
MPS II (Hunter) IDS XL DS + HS no corneal clouding ERT
MPS III (Sanfilippo) various AR HS pure CNS degeneration none
MPS IV (Morquio) various AR KS pure skeletal, normal IQ ERT (IVA)
NPD A/B ASM (SMPD1) AR sphingomyelin foam cells, lung disease olipudase (B)
NPC NPC1/2 AR cholesterol/SL VSGP, ataxia miglustat
Tay-Sachs HexA AR GM2 cherry-red spot, < 5 yr death none
Krabbe GALC AR psychosine demyelination HSCT early
CLN2 TPP1 AR lipofuscin childhood epilepsy + dementia + vision loss cerliponase IT
LAL-D / CESD LIPA AR cholesteryl esters adult: NAFLD-like sebelipase
430.2.0.2.2 Gaucher Type 1 features
  • Hepatosplenomegaly๏ผˆnear 100%๏ผ‰
  • Thrombocytopenia + anemia
  • Bone disease (pain, crisis, AVN, Erlenmeyer flask)
  • Pulmonary HTN risk (post-splenectomy โ†‘)
  • Parkinson disease risk โ†‘
  • Ferritin โ†‘โ†‘๏ผˆmisleading๏ผ‰
430.2.0.2.3 Fabry features (5 P + 2 organ)
  • Pain (acroparesthesia)
  • Purple skin (angiokeratoma)
  • Proteinuria โ†’ CKD
  • Prominent heart (LVH/HCM)
  • Premature stroke
    • cornea verticillata (slit lamp)
    • hypohidrosis
430.2.0.2.4 MPS ๅˆ†่พจ้‡้ปž
MPS Eponym Enzyme ้‡้ปž
I H Hurler IDU severe, CNS deg, corneal clouding
I S Scheie IDU mild, no CNS, mild corneal
II Hunter IDS XL, no corneal clouding
III Sanfilippo various CNS only
IV Morquio various skeletal only, normal IQ
VI Maroteaux-Lamy various Hurler-like, normal IQ
VII Sly ฮฒ-glucuronidase rare, hydrops fetalis

430.2.0.3 ๐ŸŽฏ ่‡ชๆˆ‘ๆชขๆธฌ

  1. Gaucher ้…ต็ด ? โ†’ ฮฒ-glucosidase๏ผˆGBA1๏ผ‰
  2. Gaucher ็ดฏ็ฉ substrate? โ†’ glucocerebroside
  3. Gaucher type 1 ไธ‰ๅคง่‡จๅบŠ? โ†’ HSM + thrombocytopenia + bone disease
  4. Gaucher Erlenmeyer flask in ๅ“ช้‚Š้ชจ? โ†’ ่‚ก้ชจ้ ็ซฏ
  5. Gaucher ๅขžๅŠ ๅ“ชๅ€‹็ฅž็ถ“็—… risk? โ†’ Parkinson disease
  6. Gaucher ็ฌฌไธ€็ทš tx? โ†’ ERT imiglucerase
  7. Gaucher SRT? โ†’ eliglustat๏ผˆCYP2D6 NM/IM๏ผ‰ๆˆ– miglustat
  8. Fabry ้บๅ‚ณ? โ†’ X-linked
  9. Fabry ้…ต็ด ? โ†’ ฮฑ-galactosidase A๏ผˆGLA๏ผ‰
  10. Fabry ๅ…’็ซฅๆœ€ๆ—ฉ symptom? โ†’ acroparesthesia
  11. Fabry ็œผๅพต? โ†’ cornea verticillata
  12. Fabry chaperone? โ†’ migalastat๏ผˆamenable mutations only๏ผ‰
  13. Pompe ็ดฏ็ฉ substrate? โ†’ glycogen๏ผˆlysosomal๏ผ‰
  14. Pompe IOPD vs LOPD ไธป่ฆๅทฎๅˆฅ? โ†’ cardiomyopathy at birth in IOPD
  15. Pompe ERT? โ†’ alglucosidase / avalglucosidase / cipaglucosidase+miglustat
  16. MPS I H ๅˆฅๅ? โ†’ Hurler
  17. MPS II ๅˆฅๅ + ้บๅ‚ณ? โ†’ Hunter, X-linked
  18. MPS II ๆœ€ๅคงๅทฎ็•ฐ? โ†’ no corneal clouding
  19. MPS III? โ†’ Sanfilippo, pure CNS
  20. MPS IV? โ†’ Morquio, pure skeletal
  21. NPC ็ฅž็ถ“ๅพต? โ†’ vertical supranuclear gaze palsy๏ผˆVSGP๏ผ‰
  22. NPD B ERT? โ†’ olipudase alfa
  23. CLN2 ๆŠ•่ˆ‡ๆ–นๅผ? โ†’ intracerebroventricular๏ผˆcerliponase alfa๏ผ‰
  24. LAL-D ๆˆไบบๅž‹? โ†’ CESD๏ผˆadult NAFLD-like๏ผ‰
  25. Tay-Sachs cherry-red spot ๅœจๅ“ช? โ†’ macula

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