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Cards In This Set
| Front | Back |
 Mucopolysaccharidoses-what causes this? -name the 6 lysosomal storage diseases |
 -accumulation of sulfated polysaccharides / GAGs1•Hunter syndrome2•Hurler syndrome3•Sanfilippo syndrome4•Morquio syndrome5•Maroteaux-Lamy syndrome6•Sly syndrome |
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Sphingolipidoses-what causes this?
-name the 3 lysosomal storage diseases |
-accumulation
of sphingolipid•Gaucher's disease: (accumulation
of glucocerebroside)•Niemann-Pick disease: (accumulation of sphingomyelin & cholesterol)•Gangliosidoses; Tay Sachs disease: (GM2 gangliosidosis)
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•Mucolipidoses -what causes this?-name the 3 lysosomal storage diseases
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-accumulation glycoprotein & glycolipid•I : sialidosis•II: I-cell disease•III: pseudo-Hurler polydystrophy
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 I-cell disease (Mucolipidosis II) |
 •Deficiency of N-acetylglucosamine phosphotransferase → Absense of M6P tag •Acid hydrolases lacking M6P are secreted extracellularly → Undigested substrates accumulate as inclusion bodies, progressively damages cells •Skeletal abnormalities (lack of growth) •Coarse features •Restricted joint movement •Psychomotor retardation •Enlarged liver, spleen, heart valves •Death CHF / RTI •Life expectancy <10yrs |
 Pseudo-Hurler Polydystrophy (Mucolipidosis III)- why pseudo? |
 - Milder form of I-cell - Site on enzyme that is recognized by N-acetylglucosamine phosphotransferase to put M6P tag on it is mutated - Still get some tags à some activity (lysosomal activity is totally fine otherwise) Later onset, survival into adulthood |
 Sphingolipidoses: Gaucher disease- what is deficient?-Gaucher cells?-What is a key effect? |
 - **most common lysosomal storage disease** - Deficiency of glucocerebrosidase à accumulation of glucocerebroside (a glycosphingolipid) in macrophages = Gaucher’s cells - progressive organomegaly with marrow and CNS infiltration - splenomegaly à inc destruction of blood components à anemia, neutropenia, thrombocytopenia - neurological symptoms: type I- convulsions, hypertonia, MR, apnea; type II- myoclonus, convulsions, dementia, ocular m. apraxia 75% develop visible bony abnormalities |
 Hurler’s syndrome(MucoPS IH)-Mode of inheritance?-What is deficient?-What accumulates?-Name 5 most important symptoms |
 - Most severe MPS - AR - Deficiency of α-L-iduronidase à accumulation of dermatan sulfate and heparin sulfate- Found in urine, cartilage, periosteum, tendons, valves, meninges, cornea - Initial normal growth, but at a few months old: - Physical and mental deterioration - Organomegaly, hydrocephalus - Deafness - Hirsutism - à corneal clouding! - Death Scheie & Hurler-Scheie Syndrome à milder disease |
 Scheie & Hurler-Scheie syndrome (MPS IS & MPS IHS) |
 •Residual α-L-iduronidase activity •Milder disease (Scheie = mildest MPS I) |
 Hunter’s syndrome (MPS II) |
 - Deficiency of iduronodate sulphatase - X-linked - Similar to Hurler Syndrome, but later presentation and milder course and: à NO corneal clouding! |
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Because MPC Hurlers and Hunters syndromes are so similar, what can tell them apart?
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Hurlers: -Symptoms begin at a few months-corneal clouding-Autosomal Recessive
Hunters: -Symptoms begin at 2 yrs-no corneal clouding -x-linked How to never forget?To be a Hunter, you need two eyes to aim for the X! |
 Sanfilippo syndrome (MPS III)-What is the defect?- The effects? |
 - Defect in heparan sulphate degradation (types A-D) - Normal development for first 1-2 yrs, followed by - Progressive mental retardation & increasing behavioural disturbance - Aggressive behaviour & destructiveness - Hyperactivity - Sleep disturbance (Hurler = most severe MPS... but children with Sanfilippo live longer with more severe behavioural problems) |
 Morquio syndrome (MPS IV)-What is defective? |
 - Defective degradation of keratan sulphate à deficiency of galactosamine-6-sulfatase or β-galactosidase (milder) - Short stature - Pectus carinatum (pigeon chest…Marfans) Normal IQcan be confused but it is still a lysosomal storage disease |
 Maroteaux-Lamy syndrome (MPS VI) |
 - Deficiency of arylsulphatase B Similar to Hurler but normal IQ |
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Sly syndrome (MPS VII)-deficiency?
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Deficiency
of β -glucoronidase
Wide variability in severity; different mutations
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 Specialised lysosomes Chédiak-Higashi syndrome-Mode of inheritance?-Phenotype?According to prof., What is the mutation?For USMLE purposes, what is the defect? |
 - Rare, AR - Mutation in CHS1/LYST, a lysosomal trafficking regulatory protein that is normally involved in vesicle fusion (but USMLE: defect in microtubule polymerization that causes defects in cytoplasmic granules) - Delayed fusion of phagosome w/ lysosome in leukocytes - Autophagocytosis of mealnosomes in melanocytes à albinism - Granular defects in Natural Killer cells and platelets - Recurrent infections (life threatening) - Hypopigmentatio- Mild coagulation defect- Varying neurological problems Treatment: bone marrow transplant |
