Lysosomal Storage Diseases Flashcards
Name the Sphingolipidoses Lysosomal Storage Disease
Tay-Sachs
Gauchers
Metachromatic Leukodystrophy
Fabry Disease
Krabbe Disease
Niemann-Pick Disease
What Enzyme is Deficient in Tay-Sachs Disease
Hexosaminidase A
What Enzyme is Deficient in Gauchers Disease
Glucocerebrosidase
What Enzyme is Deficient in Metachromatic Leukodystrophy
Arylsufatase A
What Enzyme is Deficient in Fabry Disease
a-galactosidase A
What Enzyme is Deficient in Krabbe Disease
Galactocerebrosidase
What Enzyme is Deficient Niemann-Pick Disease
Sohingomyelinase
What Substance Accumulates in Tay-Sachs Disease
Ganglioside GM2
What Substance Accumulates in Gauchers Disease
Glucocerebroside
What Substance Accumulates in Metachromatic Leukodystrophy
Sulfatides
What Substance Accumulates in Fabry Disease
Ceramide Trihexoside
What Substance Accumulates in Krabbe Disease
Galactocerebroside
What Substance Accumulates in Niemann-Pick
Sphingomyelin
How Does Tay-Sachs Present?
Progressive neurodegeneration, blindness, red spot on macula, early death
How does Gauchers Present?
Hepatosplenomegaly, erosion of femur, lipid-laden macrophages
How does Metachromatic Leukodystophy Present?
Demylination, dementia, early death
How does Fabry Disease Present?
X-linked-more common in boys than girls, peripheral neuropathy, progressive renal failure.
How Does Krabbe Disease Present?
peripheral neuropathy, loss of oligodendrocytes, optic atrophy, early death.
How Does Niemann-Pick Disease Present?
Progressive neurodegeneration, blindness, red spot on macula, hepatosplenomegaly, lipid-laden macrophages, early death.
What is the key clinical finding that differentiates Tay-Sachs Disease from Niemann-Pick Disease
Niemann-Pick Disease will present with hepatosplenomegaly while Tay-Sachs will not.
Which Lysosomal Storage Diseases are X-Linked?
Fabry’s Disease
I-Cell
Name the Mucopolysaccharidoses Lysosomal Storage Diseases.
Hurler Syndrome (MPS I)
Hunter Syndrome (MPS II)
What Enzyme is deficient in Hunter Syndrome?
Iduronate sulfatase
What Enzyme is deficient in Hurler Syndrome?
a-L-iduronidase
Which Mucopolysaccharidoses is more mild?
Hunter Syndrome is MORE mild than Hurler Syndrome.
What substance accumulates in Hurler Syndrome?
Heparan Sulfate, dermatan sulfate
What substance accumulates in Hunter Syndrome?
Heparan Sulfate, dermatan sulfate
How does Hurler Syndrome Present?
Crude or “unusual Facial Features,” developmental delay, cloudy corneas, heart valve problems, joint stiffness, hepatosplenomegaly, X-linked.
How does Hunter Syndrome Present?
Aggressive behavior, intellectual disability, joint stiffness, jerky movements.
Name a glycogen storage disease
Pompe Disease (Glycogen Storage Disease Type II)
What enzyme is deficient in Pompe Disease?
a-1,4-glucosidase (Acid Maltase)
Name a mucolipidosis?
I-Cell Disease (Mucolipidosis II)
What Happens in Pompe Disease?
Loss of enzyme results in an inability to break down glycogen that was captured during lysosomal autphagy-commonly in liver and muscles.
Lysosomes are packed with glycogen
How does I-Cell Disease Present
Presents like Hurler Disease
Coarse/”Unusual Facial Features,” abnormal skeletal development, restricted joint movement, corneal clouding, severe intellectual disabilities.
What enzyme miss-functions in I-Cell Disease?
Mannose is not phosphorylated by N-Acetuylglucosamine-1-phosphate transferase
Vesicles filled with acid hydrolases are transported out of cell instead to Lysosome
What is unique about I-Cell Presentation?
Blood will have high-levels of lysosomal enzymes in it.
What tissue does sphingolipidoses most affect?
Brain and Neuronal Tissue
Histologically How does I-Cell Disease Present?
Leukocytes have a large number of inclusion bodies (vesicles filled with lysosomal hydrolyses)
Lysosomes will be filled with varies debris as they cannot break anything down.
What presents first in Pompe Disease?
Children will have muscle dysfunction followed by hepatic dysfunction.
Histologically how does Pompe Disease present?
Pompe Disease presents as cells (muscle cells) filled with white dots (vesicles filled with glycogen).
