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
