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Lysosomal Storage Diseases, Lysosomes - Coggle Diagram

- - - - Lysosomal storage disease should be considered in DDx when they have these issues.
        
        Neurologic issues
        
        Renal Failure
        
        Muscular Degeneration
        
        Unexplained hepatomegaly, splenomegaly, and cardiomyopathy
        
        Skeletal dysplasia and Deformation
      - Sphingolipidoses (lipidoses) : deficiency of lysosomal enzymes, altering sphingolipid catabolism. Leads to cellular inclusions and cell dmg.
        
        Sphingolipids- normal lipid components of cell membrane; catabolized by lysosomes; accumulation cause extensive neuronal, bone, and other changes
        
        Gaucher Disease
        
        Glucocerebrosidase (Beta-glucosidase) deficiency: Prevents conversion of glucocerebroside to ceramide.
        
        3 Types
        
        Type 1 (nonneuronopathic) : most common (90% of all patients)
        
        2 more items...
        
        Fabry disease (Angiokeratoma Corporis Diffusum)
        
        X-linked deficiency of alpha-galactosidase A :star:
        
        Prevents conversion of ceramide trihexoside to glucocerebroside
        
        Accumulation of ceramide trihexoside aka globotriaosylceramide
        
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        Niemann-Pick Disease
        
        Deficient in acid sphingomyelinase activity
        
        Prevents conversion of sphingomyelin to ceramide
        
        Accumulation of sphingomyelin aka ceramide phosphorylcholine
        
        2 more items...
        
        Type C (NPC) - mutations in NPC1 and 2. Leads to accumulation of cholesterol in lysosomes.
        
        Cholesterol transport impaired :!!:
        
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        Type A ( Less than 5% sphingomyelinase activity) - severe; early onset
        
        S/sx
        
        Hepatosplenomegaly :!:
        
        1 more item...
        
        Failure to thrive
        
        Feeding Difficulty
        
        Interstitial lung disease
        
        Rapidly progressive neurodegen :!:
        
        Cherry red spot, optic atrophy, corneal clouding :!:
        
        1 more item...
        
        Death by 2-3 yr.
        
        Type B (less severe, later onset); 5-10%
        
        Little or no neurological involvement
        
        Survival into adulthood.
        
        Epidem: More common in Ashkenazi jews
      - Mucopolysaccharidoses: Results in impaired breakdown of glycosaminoglycans (mucopolysaccharides).
      - Mucolipidoses: mucolipids are complex lipid polymers containing sialic acid. Lacks the both the bottom 2.
- - - - Formation of globoid cells leads to demyel :star: :!:
        
        Demyelination and destruction of oligodendrocytes, leading to progressive demyelination.
        
        S/sx
        
        Major Mental and motor deficits
        
        Develop delay
        
        Peripheral neuropathy
        
        Hyporeflexia.
        
        Limb stiffness
        
        Opisthotonic posture :!:
        
        Head thrown back and back is extended.
        
        Optic atrophy :warning::
        
        Rx: Onset usually before 6 months.
        
        Before onset: Stem cell transplant
        
        After onset: Supportive care
        
        Note: Bc metachromatic leukodystrophy is related to the sulfatides being converted to galactocerebroside, it may have some similar Sx
        
        Optic atrophy
        
        Demyelination of CNS and PNS.
        
        Globoid cells are large multinucleated cells from mesoderm; clustered in brain
- - - - Missing develop. milestones after 6 months
      - Deterioration of cognition and motor
      - Death by 5 yr
      - Cherry red macular spot :!:
        
        Related bc blindness by around 30 months.
      - Lysosomes with onion skin. :!:
      - No hepatosplenomegaly.
- - - - Infantile Onset
        
        Motor regression and Dev delay
        
        Impaired memory
        
        Ataxia
        
        Hypotonia and hyporeflexia
        
        Optic nerve atrophy
        
        Flaccid paralysis followed by spastic paralysis :!:
      - Childhood and Juvenile Onset
        
        Ataxia
        
        Neurocognitive and Behavioral changes (worsen school performance) :!:
        
        Peripheral neuropathy
        
        Burning sensations and weakness. Distal weakness. :!:
      - Dx
        
        Arylsulfatase A test in WBC
        
        Urine sulfatide test
        
        Brain MRI (indicates hyperintensity in white matter for loss of myelin
        
        Genetic testing
        
        Treatment: Supportive care
- - - - Type: MPS 1 H
        
        Severe deficiency w/ neurodegen
        
        Often presents in infancy or early childhood
        
        Sx
        
        Chronic rhinitis
        
        Corneal clouding :!:
        
        This symptom is a big clue for any lysosomal disease.
        
        Hepatosplenomegaly.
      - Hurler has an L in it.
    - - Rx:
        
        Enzyme replacement
        
        Palliative care
        
        Bone marrow transplant
      - S/sx for both
        
        Coarse facial features :!:
        
        Previously known as Gargoylism
        
        Neurodev delays and regression :!:
        
        Joint contractures
        
        Organomegaly :!:
        
        Stiff hair
        
        Progressive respiratory insufficiency
        
        Cardiac valvular disease
        
        Cervical vertebral subluxation (misalignment of vertebra) :!:
  - - - Milder form of Hurler syndrome w/ addition of aggressive behavior and no corneal clouding
        
        Urine test: checks for unusually high lev of sugar
        
        Blood test can look at low enzyme activity
        
        Genetic testing
        
        Rx: Enzyme replacement and pallative care
        
        " A good hunter needs to see and be aggressive"
- - - - S/sx
        
        Coarse facial features
        
        Corneal clouding
        
        Failure to thrive
        
        Frequently die during childhood :!:
        
        Abnormal bone growth and restricted joint mvmt
        
        Claw hand :!!:
        
        Hepatosplenomegally
        
        Dx
        
        No glycosaminoglycans in the urine :!:
        
        Inclusion bodies in WBC :!!:
        
        Elevated blood levels of lysosomal enzymes :!:
      - Loss of M6P
        
        Lysosomal enzymes secreted extracellularly
- - - - Lipase
      - glucosidase
      - Acidic phosphatases
      - Nucleases
      - Endoproteases
- - - - Fusion of transport vesicles w/ late endosomes cause hydrolases to dissociate from M6PR. M6PR recycled to Golgi.