Diseases Flashcards
Hereditary Spherocytosis
- Description: Disease of the cytoskeleton. Type of hemolytic anemia.
- Mechanism: Defects in spectrin → loss of membrane stability.
Hutchinson Gilford Progeria Syndrome
- Description: Disease of the nucleus.
- Mech: Accelerated aging due to lack of synthesis of Lamina A (DNA/RNA synthesis)
Lysosomal Storage Disease (Tay-Sachs, Krabbe, Gaucher)
- Description: Seizures, developmental delay, movement disorders
- Mech: lack function of one or more lysosomal hydrolase → undigested material accumulates causing swelling → major impact on neuronal cells
Lufts Disease
- Description: weakness, excessive perspiration, increased basal metabolic rate, high caloric intake without increase in body weight
- Mechanism: Caused by defect in mitochondrial oxygen utilization → uncoupling of oxidative phosphorylation
Age Related Degenerative Diseases (Parkinson and Alzheimer)
- Description: Disease of the mitochondria.
- Mech: formation of free radicals (superoxides) that cause DNA damage
Zellweger Syndrome Spectrum
- Description: Disease of the peroxisome.
- Mech: Mutated PEX gene → inability to import proteins → impaired B-oxidation → increase in FAs
Dyskinesia (Kartagener’s Syndrome)
- Description: Disease of the cilia/flagella.
- Mech: Defect in motility of cilia → infections in mucus lining
- Note: May cause infertility in male. Think sperm.
Tay-Sachs
- Description: effects mostly nerve cells in the brain and spinal cord.
- Mech: The lysosomal hydrolase not present is hexosaminidase A and therefore GM2 ganglioside does not get broken down. GM2 ganglioside is important in nerve cells.
Neiman Pick
- Similar to Tay-Sachs
- Description: This disease mostly impacts neuronal cells but also causes enlargement of liver and spleen.
- Mech: effects sphingomyelin forming cells, accumulation of sphingomyelin because of lack of sphingomyelinase. The sphingomyelin accumulates in lysosomes and results in cell death.
Gaucher
- Description: most prevalent LSD. Not just nerve cells altered (liver, spleen, white blood cells, kidney, bone marrow).
- Mech: A deficiency in glucocerebrosidase which results in the accumulation of sphingolipids
I-Cell Disease
- Description: Very severe because all lysosomal hydrolases are not localized to the lysosome and instead are secreted outside the cell. Many cell types altered.
- Mech: problem with the targeting of lysosomal hydrolases to the lysosome. Tagging with mannose-6-phosphate is disrupted.
Tetanus and Botulism
Description: prevents fusion of vesicles
Mech: SNARE complex can be cleaved not allowing vesicles to bind to the plasma membrane
Receptor Mediated Endocytosis Disease
Example: LDL receptors
Description: high cholestrol
Mech: defect in LDL receptors causes high LDL in blood and increased cellular cholesterol synthesis
Malignant Hyperthermia
Description: Increased temperature due to increased metabolic activity.
Mech: Mutated RyR is sensitive to anesthetic, causing extended opening of RyR, leading to increased hydrolysis of ATP
Treatment: RyR blocker
Von Gierck’s Disease
Description: Severe hypoglycemia and weakness
Mechanism: deficiency in glucose-6-phosphatase (type 1a) or G6P transporter (type 1b) so glucose cannot be mobilized from liver
Treatment: Manageable through diet
Pompe’s Disease
Description: heart enlargement leading to cardiac arrest by age 2; autosomal inherited
Mechanism: lose alpha(1-4) glucosidase activity in lysosomes leading to increased levels of glycogen accumulation in many tissues
Treatment: no treatment
Cori’s Disease
Description: hypoglycemia weakness
Mechanism: deficiency in debranching enzyme leads to short outer branches with non-reducing ends
Treatment: glucose infusion
Andersen’s Disease
Description: liver failure and death
Mechanism: deficiency in branching enzyme leading to long
Treatment: no treatment just death
McArdle’s Disease
Description: painful cramps because muscle can not utilize glucose
Mechanism: muscle phosphorylase deficiency → cannot degrade glycogen
Treatment: liver is unaffected so mild disease
Her’s Disease
Description: nothing notable
Mechanism: mild liver phosphorylase deficiency → cannot degrade glycogen
Treatment: complete liver phosphorylase deficiency is lethal
Leber’s Hereditary Optic Neuropathy (LHON)
- Description: affects CNS, including optic nerve
- Mechanism: mutation to complex I à reduced activity to complex I à critical threshold for ATP reached à tissue failed in optic nerve
- Treatment: none discussed
Myoclonic epilepsy and ragged red fibers (MERRF)
- Description: seizure and myopathy
- Mechanism: Skeletal muscle mitochondria have crystalline arrays in them that perturb morphology and decrease cytochrome C oxidase activity.
- Treatment: none discussed
Mitochondrial encephalopathy lactic acidosis and stroke (MELAS)
- Description: lactic acidosis and stroke
- Mechanism: Skeletal muscles have ragged red fibers but no loss in cytochrome C oxidase activity.
- Treatment: none discussed
Mutations in cytochrome b of Mitochondria
- Description: exercise intolerance due to decreased activity of complex III
- Mechanism: G to A transition in the mtDNA, which is likely due to oxidation damage. Replacement of a glycine with a larger amino acid has significant effects on the overall structure.
- Treatment: none discussed
Refsum’s Disease
- Description: build up of long branched FAs which accumulate in the blood and disrupt function of neurons – attack myelin
- Mechanism: lack peroxisomal hydroxylating enzyme and leads to the accumulation of phytanic acid
- Treatment: change diet
Deficiencies in Acyl -CoA dehydrogenases
- Description: lethargy, edema, cardiac failure. Deficiencies in these enzymes can be fatal. Different enzymes for different length FAs. (VLCAD, LCAD, MCAD, SCAD). Can lead to SIDS when babies sleep at night because cannot metabolize FAs.
- Mechanism: lack of the enzyme means those affected can’t metabolize FAs
- Treatment: screening for MCAD for neonates
