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Flashcards in Lysosomal Storage Disorders Deck (16)
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describe Hurler syndrome

  • enzyme deficient: iduronidase
  • substrates accumulating: dermatan sulfate and heparan sulfate
  • urine is positive for GAGs
  • enzyme replacement therapy with iduronidase has been successful


describe Hunter syndrome

X-linked recessive

  • enzyme deficient: iduronate sulfatase
  • coarse facial features, hepatosplenmegaly, mild to moderate dev. delay, NO CORNEAL CLOUDING
  • hematopoietic stem cell therapy


what are 2 differences between Hurler and Hunter syndrome

  • Hurler = autosomal recessive, Hunter = X-linked
  • Hurler = corneal clouding, Hunter = NO CORNEAL CLOUDING


describe Tay-Sachs

  • deficient enzyme: B-hexosaminidase A
  • accumulating substrate: ganglioside (GM2) 
  • progressive neurodegeneration, development milestone delay, often regression
    • generally fatal by 2-6 years


what are clinical features of Tay-Sachs

  • EM diagram shows "onion-shell" inclusion; the lysosome looks like an onion shell
  • cherry-red spot on macula caused by GM2 accumulation


describe Gaucher disease

most common lysosomal storage disorder

  • deficienct enzyme: B-glucosidase
  • accumulating substrate: glucosyl ceramide (glucocerebroside)
    • macrophages engorged with glucocerebrosides
  • adult form (most common) sho no neurological damage but marked hepatosplenomegaly and osteoporosis of long bone


describe the cell appearance in Gaucher disease

  • crumpled tissue paper appearance of cytoplasm that is caused by enlarged, elongated lysosomes filled with glucocerebroside
  • distal femur in the shape of an Erlenmeyer flask


describe Fabry disease

X-linked recessive disorder 

  • deficient enzyme: α-galactosidase
  • accumulating substrate: globoside (aka ceremide trihexoside)
  • peripheral neuropathy, acroparesthesias (tingling and burning of extremities)


describe clinical features of Fabry disease

  • globoside accumulates in the blood vessels of skin, kidneys, nerves and heart
  • carrier females can show mild clinical features (skewed X-inactivation)


describe Niemann-Pick disease

  • deficient enzyme: sphingomyelinase
  • accumulating substrate: sphingomyelin (sphingophospholipid)
  • accumulation of sphingomyelin in the neuronal tissues
  • Type A is a severe infantile form 
    • cherry red spot in macula 
      • similar to Tay-Sachs
  • Type B appears later in childhood, presents with hepatosplenomegaly


describe cell appearnce in Niemann-Pick disease

  • deficiency of sphingomyelinase causes lipid droplet accumulation; "foamy cell" appearance


describe metachromatic leukodystrophy

  • deficient enzyme: aryl sulfatase A
  • accumulating substrate: sulfatide (rich in neurons)
  • progressive paralysis and demyelination


overview of lysosomal storage disorders


describe Pompe disease

  • a small amount of cellular glycogen is degraded by lysosomal acid maltase (1->4 glucosidase)
  • generalized accumulation of glycogen in heart, muscle, kidney and liver as vacuoles in the lysosomes (glycogen storage disorder type II)
  • enzyme replacement therapy has been successful


describe normal trafficking of enzymes to the lysosomes

  • enzymes synthesized in the ER are transported to the Golgi
  • in the Golgi, there is phosphorylation of mannose to form mannose-6-phosphate
  • enzymes that have a mannose-6-P are transported to the lysosomes
  • enzymes without the M6P are secreted by the cell
  • N-acetylglucosamine-1-phosphate transferase


describe I-cell disease

  • children with the disease have a defect in trafficking enzymes to the lysosomes
  • the Golgi failes to add the M6P marker to the enzymes destined for the lysosomes
  • these enzymes (without the M6P marker) are secreted into the bloodstream
    • high concentration of lysosomal enzymes in blood
  • accumulation of GAGs and sphingolipids in the lysosomes
  • unique feature of disease is presence of intracytoplasmic inclusions in the fibroblasts of patients; inclusion cells or I cells