Lysomal storage diseases Flashcards

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1
Q

Lysosomes break down:

A

GAGs, sphingolipids, glycogen by removing 1 sugar or whatever unit at a time

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2
Q

Hurler Syndrome

A

MPS I H (mucopolysaccharidoses)
Deficient Enzyme: (α-L-)Iduronidase (autosomal recessive)
Fxn: cleave IdUA off of dermatan sulfate and heparan sulfate
Treatments: bone marrow or cord blood transplant (before 18 months ideally), ERT
Tests: Urine positive for GAGs, fibroblast assay shows enzyme deficiency
Symptoms: Corneal Clouding, mental retardation, dwarfing, coarse (dysmorphic) facial features, upper airway obstruction, hearing loss, hepatosplenomegaly
Metabolites that accumulate: Heparan sulfate and Dermatan sulfate
Notes: More sever than hunter

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3
Q

Hunter Syndrome

A

MPS II (mucopolysaccharidoses)
Deficient Enzyme: Iduronate Sulfatase (X-linked recessive)
Fxn: Cleave sulfate from IdUA
Metabolites accumulating: Heparan and Dermatan sulfates
Symptoms: Wide range of severity, physical deformity (coarse facial features) and mental retardation are mild to severe. Hepatosplenomegaly. No corneal clouding
Tests: Uring + for GAGs and fibroblast assay
Treatments: ERT
Notes: Less severe than hurler

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4
Q

Common features of lysosomal storage disorders

A

Autosomal recessive (some are X-linked);
affect infants and young children;
hepatosplenomegaly (caused by storage of insoluble intermediates in mononuclear phagocyte system);
frequent CNS involvment (developmental delay) (not amenable to ERT as enzymes cannot cross blood brain barrier)
Cellular dysfuction (storage of undigested material, macrophage activation adn relase of cytokines)
Diagnoses by assay of enzyme in fibroblasts (or WBCs)

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5
Q

Tay-Sachs

A

Deficient Enzyme: β-Hexosaminidase A (autosomal recessive)
Class: (glyco)Shingolipidoses
Fxn: Cleave GalNAc from ganglioside GM2
Metabolites accumulating: GM2
Symptoms: Minimal hepatosplenomegaly. Progressive neurodegeration after age of 3-6 months (developmental milestone delay), blindness (gangliosides accumulate around macula leavinga white region and a cherry red spot in the middle), Onion-shell inclusions in lysosomes, usually fatal by 2-6
Tests: enzyme assay, cherry red macula
Treatments:
Notes: Especially common in Ashkenazi Jews

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6
Q

Ceramide

A

Sphingosine + Fatty acid

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7
Q

Glycosphingolipids

A

Carbohydrate moiety + ceramide

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8
Q

Shingophospholipids

A

Phospoorylcholine + ceramide

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9
Q

Gaucher Disease

A

Deficient Enzyme: β-Glucosidase
Class: (glyco)Shingolipidoses
Fxn: cleave glucose from …
Metabolites accumulating: Glucosyl ceramide (glucocerebroside)
Symptoms: macrophages engorged with glucocerebrosides (crumpled tissue paper appearance), no neruological damage (adult, most common form), hepatosplenomegaly, osteoporosis of long bone
Tests:
Treatments: ERT
Notes: Most comon lysosomal storage disorder

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10
Q

Fabry Disease

A

Deficient Enzyme: α-Galatosidase (X-linked)
Class: (glyco)Shingolipidoses
Fxn: cleave terminal galactos from…
Metabolites accumulating: Globoside (ceramide triheoside)
Symptoms: peripheral neuropathy (globoside accumulating in nerves); kidney damage, heart attack and stroke (in children) caused by accumulation in blood vessles of kidney and heart. Also accumulates in blood vessels of skin and nerves. Skin rash with ‘bathing-trunk’ distribution
Tests:
Treatments: ERT (doesn’t fix neuropathy)
Notes:

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11
Q

Niemann-Pick Disease

A

Deficient Enzyme: Sphingomyelinase
Class: (phospho)Sphingolipidoses*
Fxn: Cleave phosphoryl choline from …
Metabolites accumulating: sphyingomyelin (sphingophospholipid)
Symptoms: foamy cell appearance (lipid droplet accumulation)
Type A-infantile, more severe, primarily neurological, accumulation of sphingomyelin in neuronal tissues, cherry-red spot in macula (∴blindness), fatal in 2-3 years (similar to Tay-Sach’s)
Type B-juvenile, less severe, hepatosplenomegaly, similar to Gaucher’s
Tests:
Treatments: ERT (type B)
Notes: only disease we’re studying with phospholipid accumulation

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12
Q

Metachromatic Leukodystrophy

A

Deficient Enzyme: Aryl Sulfatase A (autosomal recessive)
Class: (gluco)Shingolipidoses
Fxn: Cleave sulfate Sulfatide–>galactosyl ceramide
Metabolites accumulating: Sulfatide
Symptoms: Progressive paralysis and demyelination
Tests:
Treatments:
Notes:

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13
Q

Pompe

A

Deficient Enzyme: Lysosomal acid maltase (1–>4 glucosidase)
Class: Glycogen Storage Disease (type II)
Fxn: Break down glycogen (break α 1, 4 bonds)
Metabolites accumulating: Glycogen
Symptoms: generalized accumulation of glycogen in heart, muscle, kidney and liver. cardiomegaly, cardiomyopathy, myopathy of skeletal muscles, hepatocellular damage
Tests:
Treatments: ERT
Notes:

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14
Q

I-cell Disease

A

Deficient Enzyme: GlcNAc Phosphotransferase (wikipedia)
Class: mucolipidosis II (wikipedia)
Fxn: Add phosphate to mannose residues
Metabolites accumulating: GAGs and sphingolipids–>lysosomal enzymes improperly tagged (no mannose-6-Pi) and are transported out of the cell instead of to lysosomes
Symptoms: intracytoplasmic inclusions in fibroblasts (Inclusion cells/I-cells), generally resmebles Hurler disease, hepatosplenomegaly, Corneal Clouding, mental retardation, dwarfing, coarse (dysmorphic) facial features, upper airway obstruction, hearing loss
Tests: high concentration of lysosomal enzymes in blood
Treatments: none really, just treat symptoms (wikipedia)
Notes:

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