Term
|
Definition
Lower pH
Hypoventilation
Decreased lung function, hypoventilation
Asthma, obesity, bronchitis, sedatives/anesthetics |
|
|
Term
|
Definition
Raise pH
Hyperventilation
Hyperventilation
Anxiety/pain, high altitude, mechanical hyperventilation |
|
|
Term
|
Definition
Lower pH
Decreased HCO3
Prolonged vomiting, excretion of HCO3, Excess H+, Using up HCO3 to buffer
Renal Failure, Methanol Poisoning, diabetic ketoacidosis |
|
|
Term
|
Definition
Raise pH
Increased HCO3
Overdose of OTC antacids
Vomiting, gastric aspiration, diuretics |
|
|
Term
|
Definition
| Fe2+ is oxidized to Fe3+; patients with a lot of HbM have bluish tint |
|
|
Term
|
Definition
| reduced synth of alpha or beta chain; reduces amount of Hb that can form anemia |
|
|
Term
|
Definition
1. Hemoglobinopathy
2. Substitution of Glu for Val in beta chain creates STICKY HYDROPHOBIC PATCH
i. In R-form patch is shielded
ii. In T-form patch exposed hydrophobic effect causes T- form to polymerize into fibers that distort RBC |
|
|
Term
|
Definition
i. Hydroxylation of Proline & Lysine requires Vit C, Fe2+ and alpha-ketoglutarate
ii. Insufficient hydroxylysine prevent proper formation of EC covalent crosslinks and glycosylation
iii. Vit C deficiency scurvy weak defective collagen |
|
|
Term
|
Definition
1. Skin hyperextensibility
2. Joint hypermobility
3. Collagen mutation
4. Bowel and arterial rupture |
|
|
Term
|
Definition
1. Demonstrates effects of protein misfolding
i. Only difference b/t prion and normal PRO is folding
2. Proteinaceous infectious particles
3. Accumulation of protease resistant isoforms in CNS
i. aggregations of amyloid plaque on the brain
4. Inherited, acquired, sporadic
5. SYMPTOMS: ataxia, dementia, paralysis
6. PrPc (normal) : 40% alpha helices
7. PrPsc (scrapies) : 45% beta sheet % 30% alpha helices
i. Examples in Humans
1. Creutzfeldt-Jako disease (CJD)
2. Kuru – 1st prion disease in humans
3. vCJD (variant CJD) – linked to BSE (bovine spongiform encephalopathy)
4. sporadic fatal insomnia |
|
|
Term
|
Definition
i. Autoimmunity to Nicotinic Ach-Receptors on NM jxn
1. Muscle weakness
2. Prevent muscle contraction
3. Treatment
a. Anticholinesterase increase Ach
b. Immunosuppressive drugs |
|
|
Term
|
Definition
narrow therapeutic window
1. Inhibits Na/K ATPase
2. Increase contractile force
3. Slow HR and respiration |
|
|
Term
|
Definition
i. Ie. Cobratoxin, conotoxin, bungarotoxin, tubocurarine
ii. BLOCK nicotinic-Ach-Receptors
1. PARALYSIS
2. Ie. Cobratoxin, conotoxin, bungarotoxin, tubocurarine
a. Treatment
3. Anticholinesterase increase Ach |
|
|
Term
|
Definition
i. Peroxisomes Synth Plasmlogens (lipids) Myelin component
ii. Zellweger Syndrome– Can’t form functional PEROXISOMES = myelination disorder
iii. Hypotonia, mental disorder, high forehead, broad, flat nasal bridge |
|
|
Term
|
Definition
i. Cystic Fibrosis
1. Loss of CFTR function
a. Cl- not transported, so H2) won’t follow
b. RESULT: accumulation of Thick mucus in lungs |
|
|
Term
|
Definition
i. cGMP phosphodiesterase inhibitor increased cGMP levels following NO release
ii. Blood vessels remain relaxed increased blood flow to penis
iii. Cialis & Levitra also cGMP phosphodieastrase inhibitors |
|
|
Term
|
Definition
i. ribosylates Gs protein causing Gs to remain ACTIVE
ii. Gs continually activates adenylate cyclase increase cAMP activate PKA phosphorylates CFTR OPEN CFTR Cl- INTO INTESTINAL LUMEN influx of H2O, Na+, HCO3-, and K+. diarrhea
iii. ARGININE on Gs is ribosylated
1. Symptoms
a. MASSIVE Diarrhea and ensuing Dehydration then Death
b. Cystic Fibrosis carriers may be less susceptible to cholera |
|
|
Term
|
Definition
i. Pertussis Toxin causes ribosylation of Gi Protein.
ii. Inhibits Gi prevents inhib of adenylate cyclase increased cAMP
iii. CYSTEINE on Gi is ribosylated |
|
|
Term
|
Definition
i. YopH is a PRO Tyr Phosphotase
ii. YopH dephosphorylate key proteins that coordinate the immune response
1. Prevents host from mounting defense |
|
|
Term
| 18. Niacin Deficiency (B3) – |
|
Definition
i. B3 provides the pyridine ring derivative of NAD/NADP, which is the site that undergoes oxidation or reduction.
1. Niacin Deficiency pellagra : symptoms – dermatitis, diarrhea, dementia, death |
|
|
Term
| 19. Riboflavin Deficiency (B2) – |
|
Definition
i. B2 provides heterocyclic ring structure of FAD/FMN that is the site involved in oxidation/reduction reactions.
1. Riboflavin is light sensitive, so treatment of neonatal hyperbilirubinemia can lead to riboflavin deficiency |
|
|
Term
| PDH Deficiency (Biotin Deficiency) |
|
Definition
a. PDH can’t convert pyruvate from CHO to form acetyl CoA => diminished ATP production via CAC
b. Pyruvate is instead reduced by NADH to form lactate
c. Causes: serum lactic acidosis
d. Fatal, neurological disorders |
|
|
Term
|
Definition
a. Beri-Beri - characterized by muscle atrophy and weakness
i. Polished rice diets lack thiamin
ii. Wet beri-beri: edema & cardiac failure
iii. Dry beri-beri: no fluid retention
b. Thiamin is required by PDH & alpha-KG-DH
c. What organs/tissues are most affected
i. Mainly the nervous system because of the reliance of the brain on CHO metabolism for energy
d. Early Symptoms: loss of appetite, constipation, nausea, fatigue, depression, peripheral neuropathy
e. Advanced Symptoms (alcoholics): confusion, ataxia, loss of eye coordination (opthalmoplegia or Wernicke-Korsakoff Syndrome)
f. Susceptible Population: Elderly, Alcoholics, Low income |
|
|
Term
| 3. DNP Uncoupling of ox-phos |
|
Definition
a. cytoplasm – DNP has O- group and H+ line the cytosolic side of the inner membrane DNP picks up H+, now OH group is permeable to membrane
b. Inner Membrane – hydroxylated DNP dissolves into the membrane DNP moves into matrix by mass action.
i. Note that the conc grad is reduced, thus free energy is lost, creating HEAT
1. Matrix –DNP carries H+ back into the matrix, dissipating the conc grad w/o ATP formation |
|
|
Term
|
Definition
Binds Fe3+ on cytochrome oxidase (complex IV) inhibiting e- transport
i. Block e- transport no e- flow to molecular O2 e- carriers fully reduced
ii. Lack of e- flow block H+ pumping by ETS complexes INHIBITION OF ATP FORMATION NADH reduces pyruvate to Lactate (lactate accumulates) lactic acidosis
iii. Same thing happens when no O2 is available to accept e- from ETS
iv. CN- Treatment
1. Rapidly administer nitrites via inhalation and injection to get CN- to release from oxidase and bind to Hb via mass action (much more Hb than oxidase)
2. Then administer sodium thiosulfate to convert CN- to non-toxic thiocyanate |
|
|
Term
|
Definition
i. Limits O2 availability no e- flow to O2 fully reduced e- carriers block H+ pumping by ETS complexes INHIB ATP FORMATION
ii. CO Treatment
1. Administer 100% O2 or hyperbaric chamber to INCREASE O2 for ETS and displace CO from Hb iron |
|
|
Term
| a. Leber’s Hereditary Optic Neuropathy (LHON) |
|
Definition
i. Sudden onset blindness due to Optic n. death
ii. Mutation of Complex I |
|
|
Term
|
Definition
i. Abnormally shaped mito w/ paracrystalline arrays
ii. Cytochrome oxidase (complex IV) activity diminished
iii. Point mutation in mitochondrial gene for Lys tRNA |
|
|
Term
|
Definition
i. Muscle specimens w/ ragged red fibers
ii. Cytochrome oxidase activity NORMAL
iii. Point mutation in gene for Leu tRNA |
|
|
Term
|
Definition
i. Measures patient compliance of glucose management
ii. Detectable for 120 days ( RBC lifespan) in blood serum
iii. Increase glucose increased HbA1c
b. AGE’s
i. PROs reduced by open chain glucose
ii. Potentially dangerous to tissues
iii. Modify EC PRO structures
c. Glucose Sorbitol
i. Sorbitol – implicated in diabetes
d. Reducing Sugar Test
i. Sugar in urine reduces substrate on test strip
ii. Indicates glucose & galactose, sorbitol |
|
|
Term
|
Definition
a. Aspartame (NutraSweet)
i. Not a sugar
ii. metabolized to Phe + Asp
b. Saccharine (Sweet n Low)
i. Not a sugar
ii. Not metabolized -- excreted
c. Sucralose (Splenda)
i. Polychlorinated sucrose
ii. Not metabolized – NO EFFECT ON INSULIN (safe for diabetics) |
|
|
Term
|
Definition
| a. Lactose is readily digested by normal flora methane gas + H+ = gas/bloating |
|
|
Term
| 9. Sucrase/isomaltase deficiency |
|
Definition
a. Diarrhea
b. If disaccharide is not cleaved it cannot be taken up by the intestines osmotically active so influx of H2O into intestine diarrhea |
|
|
Term
|
Definition
a. A sugar abundant in beans that cannot be digested by humans
1. Normal flora breakdown raffinose gas/bloating |
|
|
Term
| 11. Pyruvate Kinase Deficiency |
|
Definition
i. PEP pyruvate + ATP
ii. Regulation step of glycolysis
iii. Stimulated by: F-1,6- BPG & insulin
iv. Feedback inhibition by ATP |
|
|
Term
|
Definition
a. Enzymatic Deficiency
i. aldolase B
1. F-1-P DHAP + glyceraldehyde
ii. F-1-P accumulates in liver, with serious effects
1. Liver phosphate pools depleted and liver cannot breakdown glycogen
2. Liver tissue is damaged and liver function decreases
b. Treatment
i. Strictly fructose free diet
c. Not to be confused with Essential Fructosuria
i. Enzymatic deficiency
1. Fructokinase (liver)
2. Fructose not utilized excreted
3. Rare & HARMLESS |
|
|
Term
|
Definition
a. Failure to use galactose in glycolysis
b. Enzymatic defects
i. Galactokinase
1. Galactose Gal-1-P
ii. Gal-1-P uridyltransferase MOST COMMON
1. Gal-1-P UDP-Gal
iii. UDP Gal epimerase
1. UDP-Gal UDP-Glucose
c. Result
i. Liver damage, cataracts, intellectual disability
ii. Newborns present with feeding difficulty, jaundice, lethargy, and hepatomegaly
d. Detection
i. Galactose or Gal-P in urine
e. Treatment
i. Galactose free diet
ii. Do not breast feed |
|
|
Term
|
Definition
a. Arsenic mimics phosphate
i. Normal: 1,3- BPG 3- PG + 1ATP
ii. Arsenate: 1,3 –BPG Arsenate - 3-PG 3 -PG
1. In the presence of arsenate, glycolysis does not produce ATP!
2. Glycolysis is the sole energy source of RBCs
3. Arsenate RBC death = hemolytic anemia |
|
|
Term
| 15. How do defects in glycolytic enzymes affect RBCs? |
|
Definition
a. Result in hemolytic anemia
b. Glycolysis is the RBC main energy source
c. No ATP can’t maintain membrane potential cell death
d. F-1,6-BPase deficiency
i. Liver unable to generate glucose leads to hypoglycemia and accumulation of fat on liver
ii. F-1,6-BP –[F-1,6-BPase] F-6-P
1. This is the key regulatory step to convert F-1,6-BP to glucose
iii. Symptoms
1. Glucagon will have no ability to counter hypoglycemia, because glucose can’t be liberated from gluconeogenic pathways
iv. Treatment
1. Avoid fasting |
|
|
Term
|
Definition
i. Common in African American men
ii. X-linked recessive
iii. PPP can’t generate NADPH for reduction of glutathione in RBCs
1. RBCs become sensitive to increasing H¬2O2 levels
a. H¬2O2 causes hemolytic episodes where RBCs are inactivated by reactive O2 hemolysis when:
i. Infection: macrophages produce H2O2 and cause oxidative stress on RBCs
ii. Administration of H2O2 producing drugs (primaquine – antimalarial drug)
iii. Consumption of Fava Beans |
|
|
Term
|
Definition
a. Defective G-6-Pase
b. Can’t export glucose |
|
|
Term
|
Definition
a. Deficient acid maltase (alpha-glucosidase)
i. Required for degradation of glycogen that accumulates in the lysosome
ii. Cells swell up and die cardiac or respiratory failure |
|
|
Term
| 3. Type III: Cori Disease |
|
Definition
a. Defective glycogen branching enzyme
i. Only non-branched outer layers of glycogen can be degraded. Glycogen still forms branches, but can’t debranch them, so glycogen granules become large |
|
|
Term
| 4. Type V: McArdle Disease |
|
Definition
a. Defective glycogen phosphorylase
i. Unable to utilize stored glycogen
ii. Exercise causes muscle cramps due to inability to use glycogen to supply energy for muscle
iii. Greater than normal glycogen stores |
|
|
Term
|
Definition
Dermatan sulfate
Heparin sulfate Iduronate sulfatase XR
Skeletal abnormalities, intellectual disability |
|
|
Term
|
Definition
Dermatan sulfate
Heparan sulfate a-iduronase
Treatment: enzyme replacement therapy AR
Skeletal abnormalities
Intellectual disability |
|
|
Term
|
Definition
Heparan sulfate
Various defects in heparin sulfate degradation AR
Severe intellectual disability |
|
|
Term
|
Definition
i. Carnitine is needed to import FAs into mitochondria
ii. Symptoms:
1. Hypoglycemia with no detectable rise in ketone levels
a. Under these conditions most FA cannot be broken down to acetyl CoA or respond to hypoglycemia by producing ketone bodies.
2. Lethargy because cells aren’t able to utilize energy from FA metabolism.
3. Hepatomegaly because fat is stored in liver |
|
|
Term
| 20. MCAD Deficiency (Medium Chain Acyl DH) |
|
Definition
i. Most common Acyl CoA deficiency
ii. Clinical Presentation: non-ketotic hypoglycemia (life-threatening)
iii. Can’t degrade medium chain acyl-CoA chains to small chain acyl-CoA for transport across mito membrane ACCUMULATION OF MEDIUM CHAIN ACYL-CoA |
|
|
Term
|
Definition
| i. accumulation of undegraded phytanic acid neurological defects |
|
|
Term
| 22. Peroxisomal Biogenesis Problems |
|
Definition
i. Zellweger Syndrome
1. Can’t form functional peroxisomes decreased capacity for very long chain FA oxidation
2. Diagnosis: Accumulation of 24-26-carbon FAs
3. Result: myelination disorder
4. Symptoms: neurological defects
b. Plasmalogens contain a fatty alcohol
c. Immune system, brain, and heart are rich in plasmalogens
d. Synthesis occurs in peroxisomes
i. Synthesis of Plasmalogens
1. Acyl transfer to C1 of DHAP
2. Acyl group exchanged for fatty alcohol
3. C2 of DHAP reduced then acyl group to C2 (from acyl-CoA)
4. Remove phosphate from C3 choline to C3 (from CDP-choline)
5. choline plasmalogens |
|
|
Term
| 23. acute fatty liver of pregnancy |
|
Definition
a. Symptoms: jaundice, nausea, enlarged liver
b. Biopsy: large fat inclusions in cytoplasm of liver parenchymal cells
c. Diagnosis: Acute fatty liver of pregnancy
d. Cause: Deficiency of hydroxyacyl-CoA DH
i. Stalled degradation of long chain FAs fat accumulation |
|
|
Term
| 24. development of a fatty liver in chronic alcoholism |
|
Definition
a. 3 Factors
1. High [NADH] blocks from EtOH metabolism blocks CAC enzymes and forces acetyl CoA into FA synthesis fat deposition on liver
2. B-hydroxyacyl DH requires NAD+ Lack of NAD+ slows FA degradation fat deposition on liver
3. Damaged liver has REDUCED capacity to SYNTHESIZE VLDLs to transport FAs to adipose tissue fat deposition on liver |
|
|
Term
| 25. NSAIDs and corticosteroids |
|
Definition
| a. Inhibit prostaglandin synthesis at the level of phospholipase A2 & COX |
|
|
Term
|
Definition
| a. Lipoxygenase inhibitor prevent the synthesis of LTC4 & LTD4 which promote smooth muscle contraction of airways |
|
|
Term
| 27. prevention of respiratory distress syndrome in premature infants |
|
Definition
a. Surfactant is rich in phospholipids, particularly dipalmitoyl PC
b. No PC no surfactant |
|
|
Term
|
Definition
| B-hexosaminidase Ganglioside Gm2 Blindness, cherry red spot macula, ID |
|
|
Term
|
Definition
B-cerebrosidase Glucocerebroside Liver & spleen enlargement
Erosion of bone |
|
|
Term
|
Definition
a-galactosidase
Ceramide trihexoside Skin rash, kidney failure |
|
|
Term
|
Definition
| Sphingomyelinase Sphingomyelin Liver & spleen enlargement, ID |
|
|
Term
|
Definition
| B- hexosaminidase A & B Gm2 ganglioside, globoside Like Tay Sachs, but progresses faster |
|
|
Term
| Metachromatic leukodystrophy |
|
Definition
| Arylsulfatase Sulfatide ID |
|
|
Term
|
Definition
| absence of glycosidases accumulation of glycolipids in lysosomes of phagocytic cells (found in liver, spleen, CNS tissue, and bones |
|
|
Term
|
Definition
| absence of proteoglycan-degrading enzymes proteoglycan accumulation in lysosomes |
|
|
Term
| 30. Gaucher’s Disease, (a type of sphingolipidoses) |
|
Definition
a. Cause: Absence of glucocerebrosidase accumulation of glucocerebrosides in liver, spleen, CNS tissue, & bones
b. Symptoms: bone pain, stunted growth, enlarged spleen |
|
|
Term
| 31. regulation of cholesterol synthesis and the action of statins |
|
Definition
a. Regulation of cholesterol: occurs at the RLS
i. HMG-CoA –[HMG-CoA reductase] mevalonic acid
1. HMG-CoA Reductase regulated by phosphorylation and by cholesterol
ii. Inactivation
1. AMP-dependent Kinase inactivates HMG-CoA Reductase
2. High cytoplasmic [cholesterol] inactivates HMG-CoA Reductase
3. REDUCED BY STATINS
iii. Activation
1. Insulin-dependent phosphorylase activates HMG-CoA Reductase |
|
|
Term
|
Definition
a. Bile contains
i. Cholesterol
ii. Bile salts
iii. Phospholipids
b. High [cholesterol] of bile precipitation of cholesterol stones get stuck in gall duct |
|
|
Term
|
Definition
a. Pathology:
i. High serum cardiac troponin
ii. ECG abnormalities
iii. Elevated serum cholesterol & TGs
b. Cause: defective LDL receptor
Interesting side note: xanthomas of the knuckles and thickened Achilles tendon may indicate persistent hypercholesterolemia/hyperlipidemia |
|
|
Term
|
Definition
inappropriate immune response to α-gliadin a glycoprotein in gluten
i. Reduces absorptive area of small intestine
ii. Symptoms
1. Nutrient deficiency – due to reduced absorptive area of small intestine
2. Abdominal cramps and bloating
iii. Treatment
1. Strict avoidance of gluten (a-gliadin) |
|
|
Term
|
Definition
i. Enzymes are activated inside the pancreas rather than the duodenum.
ii. Cause
1. Alcohol
2. Infections
3. Gallstones
iii. Treatment
1. Fasting (avoid stim. of enzymes)
2. Supportive in nature |
|
|
Term
|
Definition
a. Genetic defect of large aa transporters
i. malabsorption of large neutral aa’s
ii. Same transporters also found in proximal tubules of kidneys
b. Symptoms
i. Pellagra
ii. Neutral aa’s in urine
c. Treatment
i. Niacin supplementation |
|
|
Term
|
Definition
i. Pressure ulcers are localized areas of soft tissue breakdown
ii. Cause
1. Local tissue ischemia
2. Malnutrition
iii. Treatment
1. High protein nutritional support rich in Arginine
a. Nuts & seafood
b. Arg is a precursor for No an creatine |
|
|
Term
| 5. Elevated AST (aspartate) |
|
Definition
i. AST found in liver, heart, muscle, kidney (in descending order of concentration)
ii. Indicator of liver damage…but may also indicate myocardial infarct and other conditions
iii. OAA + Glu (AST) a-KG + Aspartate |
|
|
Term
| 6. Elevated ALT (alanine) |
|
Definition
i. ALT found primarily in Liver
ii. More specific indicator of liver damage
iii. Alanine(ALT) Pyruvate
b. Which is the more specific marker for hepatic damage? Why?
i. ALT is a more specific indicator of liver damage b/c it is found primarily in the liver |
|
|
Term
|
Definition
a. How does PKU get its name?
i. Phenylketonuria unable to convert Phe Tyr
ii. Excess Phe converted to phenylpyruvate (for disposal)
iii. Urine is high in phenylpyruvate
b. What 2 different enzyme defects can cause PKU?
i. Phe Hydroxylase
ii. DHBtn Reductase
c. What is the metabolic basis for PKU pathology?
i. Missing/ defective Phe Hydroxylase or DHBtn Reductase
d. Treatment
i. Low Phe diet supplemented with Tyr
e. Why should patients with PKU avoid aspartame (Nutrasweet)?
i. Aspartame Asp + Phe + methanol
1. Patients with PKU accumulate phenylpyruvate which causes brain damage |
|
|
Term
|
Definition
a. Deficiency of B12 N5-methyl-THF accumulation
b. Deficiency of B12 decrease in oxidized form of THF, N5, N10 methylene-THF, which is required for synthesis of thymidine and purine rings prevent DNA replication MEGALOBLASTIC ANEMIA |
|
|
Term
|
Definition
a. Causes
i. Deficient Vit B12 intake
ii. Lack of intrinsic factor (produced by parietal cells in stomach)
iii. Inability to absorb (ileum)
iv. Lack of transcobalamin (transport)
b. Demyelination Neurological problems
i. 2 theories for why demyelination occurs
1. Defective Methylmalonyl-CoA mutase causes branch chain FAs to incorporate into myelin demyelination
Odd-chain FAs propionyl COA D- methylmalonyl CoA L-methylmalonyl CoA --(B12/mutase) succinyl CoA
2. Defective Methionine synthase – unknown mechanism, but patients treated successfully with methionine supplementation
Homocysteine + N5 methyl THF –(B12/methionine synthase) Met + THF |
|
|
Term
|
Definition
a. High [homocysteine] atherosclerosis
i. Homocysteine
1. has a toxic effect that damages the endothelial cells of blood vessels
2. it oxidizes LDL
3. Interferes with blood clotting system
b. Homocysteine requires B6, B12, and folate….B vit supplementation lowers homocysteine levels, but has not been shown to prevent atherosclerosis |
|
|
Term
| 11. maple syrup urine disease? |
|
Definition
a. Defective BCKDH (branched chain a-ketoacid DH)
b. Can’t break down branched chain a-ketoacids makes urine smell like maple syrup
c. Symptoms
i. Poor feeding
ii. Vomiting
iii. Slow, irregular breathing
iv. Ketoacidosis
v. Hypoglycemia
vi. Neurological damage
vii. Death
d. Treatment
i. Dietary restriction on sources of BCAA
1. However, some essential amino acids are BCAAs
ii. Infants die w/in 4-7 days if untreated
iii. Common in Mennonites |
|
|
Term
| 12. SEVERE HYPERAMMONEMIA |
|
Definition
1. Carbomoyl phosphate synthase I defect
2. Ornithine transcarbomoylase defect
ii. Liver Disease patients cannot metabolize ammonia generated by breakdown of nitrogenous compounds in food hyperammonemia
iii. Symptoms
1. Lethargy
2. Stupor
3. Vomiting
4. Convulsions
5. Swelling of brain (astrocytes)
a. Astrocytes are site where Glu + NH4+--(Glutaminase) Gln
b. Glu is a common NT in brain. So it is released by neurons then picked up by astrocytes and converted to Gln as shown above.
c. During hyperammonemia there is an increase in Gln inside the astrocytes, which cause water influx into the cells
i. This is an elementary explanation – mechanism is complex and poorly understood
b. TREATMENT of HYPERAMMONEMIA: 2 drugs
1. Phenylbutyrate phenylacetate phenyl acetyl-CoA + Gln phenylacetylglutamine (water soluble and excreted through kidney; eliminates 2 nitrogen)
2. Benzoate benzoyl CoA + Gly hippurate (water sol. And excreted via kidney ; eliminates 1 nitrogen)
*Net result is to pull nitrogen from the usual urea cycle precursors into Gly and Gln, which are eliminated as conjugates via the kidney |
|
|
Term
|
Definition
i. defective tyrosinase¬¬ no melanin
ii. Tyr –(tyrosinase) DOPA dopaquine colored melanin |
|
|
Term
|
Definition
a. Niacin deficiency
i. Cause
b. defective IDO
c. Try deficiency Tryptophan –(IDO) niacin
1. iron, riboflavin, and pyridoxine deficiency
d. Symptoms
i. Dermatitis, Diarrhea, Dementia, Death |
|
|
Term
| 15. refeeding a starved patient |
|
Definition
a. 2 conditions to consider
i. Severely starved patients lack digestive enzymes
1. Can’t breakdown dietary CHO diarrhea
ii. Intracellular phosphate stores depleted
1. Shift from CHO metabolism to gluconeogenesis/ ketogenesis depletes phosphate stores
2. Reintroducing CHO starts glycolysis consumes large amt of phosphates (soaks up phosphate from serum)
3. Hypophosphatemia ensues! Then death.
b. Always watch electrolytes, especially phosphate when refeeding a starved patient. |
|
|
Term
| 16. obese patients experience starvation |
|
Definition
a. Metabolic processes require phosphate, which is obtained from the diet.
No phosphate starvation |
|
|
Term
|
Definition
a. First 10-20 minutes: muscle function driven by ATP/ creatine phosphate reserves
b. 20- 120 minutes: muscle function supported by mix of FA and glucose metabolism
i. 60 min: 50% depletion of liver glycogen
c. Over 120 min: glycogen stores exhausted – energy almost exclusively from FA beta oxidation |
|
|
Term
| 18. Type 1 (juvenile or insulin dependent diabetes mellitus (IDDM)) |
|
Definition
i. Cause:
1. Autoimmune destruction of insulin producing, pancreatic beta cells
a. Possibly triggered by viral infection causing immune system to attack beta cells
b. Genetic factors
ii. Prevalence:
1. 10-20% of total cases of diabetes
iii. Treatment:
1. Exogenous insulin in correct amount |
|
|
Term
| 19. Type 2 (adult onset or non-insulin dependent diabetes mellitus (NIDDM)) |
|
Definition
i. Cause:
1. Insulin resistant target tissues
a. Consequence of chronic hyperalimentation (overeating)
i. Overloads capacity to remove glucose from circulation
b. Insulin concentration usually very high
2. Central obesity & sedentary lifestyle
3. Genetic factors
ii. Prevalance:
1. 90% of total cases of diabetes
iii. Treatment:
1. Weight loss & exercise
2. Drug therapy
a. Stimulate insulin secretion
b. Sensitizing peripheral tissue to insulin
c. Reduce intestinal absorption of glucose
d. Repress gluconeogenesis (review of regulatory targets below) |
|
|
Term
|
Definition
i. Cause:
1. Insulin sensitivity of mother is down-regulated (normal)
a. Allows fetus to compete for glucose
2. Problem: TOO MUCH DOWNREGULATION
a. Causes birth defects and fetal overgrowth
ii. Treatment:
1. Maternal glucose levels monitored closely during pregnancy |
|
|
Term
|
Definition
i. Typical of Type 2 diabetes
ii. High serum [glucose] high osmotic pressure draws water from tissues dehydration results
1. Excess water excreted by kidney polyuria
2. Thirsty b/c body tries to rehydrate polydipsia
3. Dehydration + hyperglycemia affect CNS confusion & disorientation (non-ketotic hyperosmolar syndrome (NKHS) or hyperosmolar hyperglycemic state (HHS))
a. Extreme cases cause NKHS coma (NKHHC)
b. Treatment of NKHHC:
i. fluid administration and fluid replacement
ii. Serum potassium must be watched at all times!
1. Potassium lost during periods of fluid loss
2. Insulin forces potassium into cell, so serum potassium will drop after insulin admin |
|
|
Term
|
Definition
i. Insulin insufficiency hyperlipidemia (increased VLDLs, chylomicrons, & FFAs)
1. Lipoprotein lipase (LPL) is regulated by insulin
a. Insufficient insulin LPL remains INACTIVE lipids not released from VLDL or chylomicron lipoproteins increase
ii. Insufficient insulin hormone sensitive lipase (HSL) remains ACTIVE
1. Adipocytes continually release FAs into circulation liver takes up FAs integrates FAs into VLDL further increased circulating VLDL |
|
|
Term
|
Definition
ii. Diabetic Ketoacidosis (DKA) – consequence of unrestrained lipolysis and ketone production
iii. Insulin represses ketone production by:
1. Insulin inhibits lipolysis by inhibiting HSL
2. Insulin inhibits transport of FAs into mitochondria
REVIEW: FA Transport into mitochondria
a. SHORT FFAs (up to 10 Cs) can cross mito membrane w/o help
b. MEDIUM-LONG FFAs (12 Cs and up) are regulated by a 3 step process
i. Coenzmye A activate FAs (requires ATP)
1. FA + CoA + ATP –[Acyl-CoA Synthetase] Acyl-CoA + AMP + PP
ii. Carnitine
1. CPT 1 (carnitine-palmitoyltransferase) in OUTER Mito membrane transfers acyl-group from CoA to Carnitine
a. Acyl-CoA + carnitine acyl-carnitine + CoA
2. Translocase in inner mito membrane moves acyl-CoA into matrix
a. Acyl CoA –[translocase] into matrix
iii. Re-synthesis of acyl-CoA
1. CPT 2 in inner mito membrane transfers acyl group from carnitine back to CoA
iv. No insulin no inhibition of ketone synthesis ketoacidosis
v. Patients present with hyperglycemia, nausea, vomiting, abdominal pain
vi. High serum [glucose] dehydration (watch for potassium loss through kidney)
vii. Treatment:
1. Fluid replacement
2. Correction of hyperglycemia and acidosis
*Insulin admin lowers serum glucose AND potassium |
|
|
Term
|
Definition
i. High serum [glucose] damage walls of blood vessels
1. Large vessel damage stroke and MI
2. Small vessel damage cuts off blood supply to peripheral tissue necrosis of:
a. Retina blindness
b. Nephrons kidney failure |
|
|
Term
| 25. Acute Intermittent Porphyria (AIP) |
|
Definition
i. Deficient PBG deaminase
ii. ALA & PBG accumulate in blood and urine (dark red)
iii. Symptoms
1. Confusion, sharp abdominal pain, death |
|
|
Term
| 26. Porphyria Cutanea Tarda (PCT) |
|
Definition
i. Deficient UPG decarboxylase
ii. Porphyrins accumulate – detected in urine
1. Pink fluorescence under UV light
iii. Symptoms
1. Photosensitivity – due to porphyrins absorbing UV light creates O2 radicals in tissue |
|
|
Term
|
Definition
i. Inhibits PBG synthase & ferrocheletase
ii. ALA & other heme precursors accumulates
iii. Symptoms
1. Similar to the porphyrias
28. alcohol and certain drugs trigger porphyria attack
a. Alcohol/drugs induce cytochrome synthesis creates demand for heme.
b. Patients that already suffer from porphyria cause a buildup of synthesis intermediates, and trigger an acute porphyria attack. |
|
|
Term
| 29. Prehepatic (hemolytic) Jaundice |
|
Definition
i. Elevated RBC destruction high serum [bilirubin] exceed liver capacity for glucoronation and excretion
ii. High [INDIRECT BILIRUBIN]
iii. Examples
1. Neonatal physiological jaundice
2. Hemolytic diseases |
|
|
Term
| 30. Hepatocellular Jaundice (Liver Disease) |
|
Definition
i. Liver disease impairs function of glucoronation
ii. High [INDIRECT BILIRUBIN]
iii. Characteristics
1. Pale color feces & urine
2. Mostly unconjugated bilirubin in tissues and serum
3. ALT & AST in serum
iv. Common Causes
1. Acetaminophen poisoning
2. Hepatitis |
|
|
Term
| 31. Cholestatic Jaundice (obstruction) |
|
Definition
i. Obstructed biliary duct impairs excretion of conjugated bilirubin
ii. High [CONJUGATED BILIRUBIN]
iii. Characteristics
1. Pale color feces DARK urine
2. Alkaline phosphatase in serum
iv. Causes
1. Gallstones
2. Neoplasia
3. Cirrhosis |
|
|
Term
|
Definition
1. Reduced excretion (most common)
a. Renal insufficiency
b. Metabolic acidosis (competition b/t uric acid and organic acids for excretion)
2. Increased production
a. Increased nucleotide turnover (hemolytic disease, chemotherapy)
b. Diets rich in purine
3. Alcohol consumption both increases production & reduces excretion
a. Liver damage rapid turnover of ATP & increase serum lactic acid
4. Hyperuricemia leads to gout and kidney stones |
|
|
Term
|
Definition
i. Uric acid is relatively insoluble
ii. Exists as urate ion in serum
iii. Sodium urate crystals deposit in joints of extremities
iv. Symptoms
1. Pain
2. Joint swelling
v. Generally only one joint affected MP joint of 1st toe
1. Other joints can be affected:
a. tarsal joints
b. ankles
c. knees |
|
|
Term
|
Definition
| i. High [uric acid] deposition in kidney |
|
|
Term
|
Definition
acts to reduce uric acid levels
a. Allopurinol oxypurinol
i. Oxypurinol comp. inhibits xanthine oxidase
1. Xanthine –(xanthine oxidase)uric acids |
|
|
Term
|
Definition
a. Defect in UMP Synthase Orotic acid accumulation
b. Inability to synthesize pyrimidines
i. Megaloblastic anemia
ii. defects in cell immunity
c. Treatment
i. Pyrimidine supplementation |
|
|
Term
|
Definition
block cell proliferation
a. Hydroxyurea Inhibits ribonucleotide reductase
i. Blocking ribonucleotide reductase NO dNTP synthesis no cell proliferation
ii. Important cancer chemotherapy agent |
|
|
Term
| 36. severe combined immunodeficiency (SCID) |
|
Definition
a. Impacts B & T Cell function
b. Mutated adenosine deaminase
i. Adenosine—(adenosine deaminase) inosine
ii. Build-up of adenosine metabolites
1. Increased dATP inhib ribonucleotide reductase
a. Blocks purine pyrimidine inadequate cell proliferation inadequate immune responses |
|
|
Term
|
Definition
a. 5-FU (a uracil analog w/ flourine)
i. Thymidilate synthase inhibitor
ii. 5-FU FUMP FUTP is incorporated into RNA
1. FUDP –(ribonucleotide reductase) FdUDP FdUMP
a. FdUMP + N5, N10 methylene covalently bind thymidylate synthase IRREVERSIBLE INHIBITION of thymidylate synthase decrease dTTP & increased dUTP & increase FdUMP
i. DNA strand breakage & cell death |
|
|
Term
|
Definition
a. Deficient HGPRTase
b. Symptoms
i. Hyperuricemia
ii. Kidney stones
iii. Intellectual disability
iv. Self destructive biting of fingers and lips |
|
|
Term
|
Definition
Hypoxanthine + PRPP IMP + PPi
Guanine + PRPP GMP + PPi
HGPRTase
1. Decrease de novo synthesis of purines by consuming PRPP
2. GMP inhibits amidophosphoribosyltransferase
(enzyme of purine synth committed step) |
|
|
Term
|
Definition
yet has low toxicity in the human body
a. 5-FC
i. Antifungal agent
ii. Fungi express cytosine deaminase
1. 5-FC –(cytosine deaminase) F5-U
a. FU (a uracil analog w/ flourine)
i. Thymidilate synthase inhibitor
1. 5-FU FUMP FUTP is incorporated into RNA
2. FUDP –(ribonucleotide reductase) FdUDP FdUMP
3. FdUMP + N5, N10 methylene covalently bind thymidylate synthase IRREVERSIBLE INHIBITION of thymidylate synthase decrease dTTP & increased dUTP & increase FdUMP
4. DNA strand breakage & cell death death of FUNGI
iii. Human cells cannot deaminate cytosine so the drug has low toxicity |
|
|
Term
| 40. Causes of elevated serum alkaline phosphatase (AP) |
|
Definition
i. Liver disease
1. AP secreted by cells lining gall duct
2. Obstructive gall duct INCREASES serum AP
3. Also have high bilirubin
ii. Bone disease
1. AP secreted during bone remodeling
2. Increased bone remodeling INCREASES serum AP |
|
|
Term
| 41. abnormal albumin concentrations |
|
Definition
a. Albumin produces by liver Binds hydrophobic stuff (steroid hormones, FAs, indirect bilirubin) and Ca2+
i. Maintains oncotic pressure
b. Low serum albumin
i. Manifests as edema b/c water osmotically drawn into tissue … not enough albumin in serum to pull water into circulation, so water goes where the proteins are pulling hardest, the tissue
ii. Caused by Liver Disease |
|
|
Term
| 42. Causes of abnormal serum potassium |
|
Definition
i. High K+
1. Decreased excretion
a. Renal insufficiency
ii. Low K+
1. Increased loss due to excretion by GI or kidneys
a. Diarrhea
b. Diuretics |
|
|
Term
| 43. high serum BUN/creatinine levels |
|
Definition
a. High Blood Urea Nitrogen (BUN)
i. If PRO intake and catabolism are normal, elevated BUN may indicate impaired renal excretion
b. High serum creatinine |
|
|
Term
| glomerular filtration (GFR)problem |
|
Definition
|
|
Term
|
Definition
a. CRP made by liver
b. Marker of acute response to injury
c. Useful for following healing process; sudden rise in CRP es no bueno |
|
|
Term
| 46. myocardial infarctions |
|
Definition
b. Myoglobin –
i. very high immediately after MI
ii. NOT heart muscle specific
c. Creatine Kinase (CK-MB)
i. Cardiac isozyme of creatine kinase (CK-MB)
ii. Detectable very early after MI
iii. Disappears quickly
d. AST
i. Released a little later than CK-MB
e. *Troponins (TnC)
i. Most sensitive marker of MI
ii. Detected very early
1. If 12 hrs after onset of chest pain there are no troponins no MI
f. Lactate DH (LDH)
i. Cardiac isoform of lactate DH
ii. Released several days after MI
g. Onset of MI determined by ratio of serum enzymes |
|
|
Term
|
Definition
a. Urine analysis
i. Check for hyperglycemia
b. HbA1c reflection of 120 day glycemic control
i. High HbA1c poor glycemic control
c. C-Peptide measure endogenous insulin production
i. Higher C-Peptide higher insulin production |
|
|
Term
| 48. kidney and liver function tests |
|
Definition
a. Kidney Disease
i. High BUN & creatinine renal failure
ii. Low urine osmolality renal failure
iii. Excretion of Na+ and K+ normalized to creatinine excretion |
|
|
Term
|
Definition
i. Bilirubin
ii. ALT/AST
iii. Alkaline phosphatase |
|
|
Term
|
Definition
a. Reperfusion – sudden reintroduction of oxygen to hypoxic tissue burst of ROS that damage membranes, PROs, & DNA
i. Causes:
1. Reactive Oxygen Species (ROS)
2. Vascular injury
3. Alterations in Ca2+ handling
4. Altered myocyte metabolism
5. Inflammatory response
ii. Intervention ( though ineffective in clinical trials)
1. Antioxidant therapy (Vit E) |
|
|
Term
|
Definition
generates oxidative stress
a. Excessive iron generates HOˑ which damages hepatocytes & other tissues
IRON – bound to ferritin
O2 + Fe2+ O2- + Fe3+
H2O2 + Fe2+ HOˑ + HO- + Fe3+
b. Treatment
i. Bleeding patient decreases iron & increases iron consumption during regeneration of Hb for RBCs
ii. Chelation of serum iron (bind it to something else) |
|
|
Term
|
Definition
a. Gene family clustered at one ch’somal locus
b. Ex. B-globin gene family
i. Hydroxyurea
1. used to treat sickle cell anemia
2. stimulates expression of fetal copies of B-globin gene in adults compensates for defective copy of gene in adult |
|
|
Term
| 2. nalidixic acid & ciprofloxacin (antibiotic) |
|
Definition
a. acts on Bacterial Topoisomerase II
i. manipulates 2 intact double helices at a time. Introduces transient double strand break in one double helix, then directs the other double strand through opening and relegates it at site of cut. |
|
|
Term
| 3. doxorubicin (anticancer) |
|
Definition
a. Acts on Human Topoisomerase II
i. manipulates 2 intact double helices at a time. Introduces transient double strand break in one double helix, then directs the other double strand through opening and relegates it at site of cut |
|
|
Term
| 4. Azoospermic Male (Meiosis arrest) |
|
Definition
1. No sperm in semen
2. No synaptonemal complex Failure of sperm to complete meiosis I
no mature sperm |
|
|
Term
| 5. Xeroderma Pigmentosa (XP) |
|
Definition
a. Cause:
i. Errors in nucleotide excision repair cause
1. errors in helicase, DNA polymerase, or DNA ligase
b. Effect
i. extreme sensitivity of skin to sunlight
ii. pigmentation changes
iii. skin cancer on areas exposed to sun |
|
|
Term
|
Definition
a. Proportional dwarfism, keel shaped face, photosensitivity, immunodeficiency, reduced fertility, predisposition to many malignancies
b. Mutation in BLM gene encoding for DNA helicase
i. Defective DNA replication
ii. Replication fork progression and processing of Okazaki fragment delayed |
|
|
Term
| 7. HNPCC [Heritable Nonpolypsis Colorectal Cancer] (Lynch Syndrome) |
|
Definition
| a. Caused by defect in mismatch repair system |
|
|
Term
| 8. Cytarabine (Cytosar-U or Tarabine PFS) |
|
Definition
a. An analogue of cytidine that contains arabinose in place of ribose
b. Converted to cytarabine triphosphate inside cells
i. Competes for binding to DNA polymerases blocks replication
ii. Treatment for leukemia |
|
|
Term
| 9. Cyclophosphamide (Cytoxan or Neosar) |
|
Definition
a. Is a pro-drug
i. Cyclophosphamide –[liver] phosphoramide mustard
ii. Phosphoramide mustard is a bifunctional alkylating agent
1. Forms DNA crosslinks programmed cell death
b. Treatment for Hodgkins Lymphoma, lung, breast, and testicular cancer |
|
|
Term
| 10. Doxorubicin (adriamycin) |
|
Definition
a. Anthracycline antibiotic
b. Forms complex w/ DNA & topoisomerase II
i. Topoisomerase passes one double stranded segment of DNA through an enzyme mediated break in the double strand
ii. Relieves supercoiling
c. Doxorubicin prevents re-ligation of double strand break programmed cell death |
|
|
Term
| 11. toxin-α-amanitin functions |
|
Definition
a. Death Cap Mushroom
i. Inhibits Pol II blocks mRNA synthesis
ii. Symptoms
1. Initial: mild GI distress
2. 48 hours: massive liver failure
a. Essential liver PROs & their mRNAs degraded by normal processes cannot be replaced b/c of Pol II inhibition
iii. Treatment
1. Support
a. Gastric lavage (emptying)
b. Activated charcoal removes unabsorbed toxin & interrupts hepatic circulation of toxin
2. 20-40% fatality w/o Liver transplant |
|
|
Term
|
Definition
a. Found is streptomycetes in soil
b. Inhibit Pol II in BACTERIA, but not eukaryotic Pol II
c. Effective against Mycobacterium tuberculosis |
|
|
Term
|
Definition
= reduced synth of β-chain of Hb
i. results in anemia
Cause
ii. Incorrect splicing of pre-mRNA
1. Β0 mutation destroys normal acceptor site at end of intron 2
a. Result mRNA no longer codes for β-globin gene
2. β+ mutation that creates new acceptor site in intron 1
a. Result mRNA no longer codes for β-globin gene |
|
|
Term
| 14. Rubenstein-Taybi syndrome |
|
Definition
a. Increase cAMP increase PKA phosphorylate CREB binds CRE recruits CBP aka CREBBP recruits EP300
i. CBP & EP300 function as HATs acetylate histone relax chromatin TXN ON
b. Rubenstein-Taybi
i. Mutated CBP or EP300 NO TXN |
|
|
Term
|
Definition
a. Estrogen receptor is an activator of TXN
b. Some breast cancer cells are ER+, evidence that estrogen is responsible for aberrant cell growth during puberty
c. Tamoxifen is a comp. inhib of estrogen inhibits tumor growth |
|
|
Term
|
Definition
1. *Streptomycin binds small subunit inhib initiation & cause mistranslation
2. *Neomycin/gentamycin binds ribosomes and cause mistranslation
3. *Tetracycline blocks A-site & prevents tRNA binding
4. Chloramphenicol prevents peptide bond formation b/t 1st & 2nd aa(Step 3 Elong) |
|
|
Term
|
Definition
1. Ricin glycosidase that removes adenine bases from rRNA in large subunit
2. Diptheria toxin inactivates EF2 by ADP ribosylation
EF2 + NAD Diptheria Toxin ADP-ribosyl EF2 + nicotinamide |
|
|
Term
| 18. Charcot Marie Tooth Disease |
|
Definition
a. Mutated Heat Shock PROs
b. Chaperones repair PRO damage from heat & other stresses that unfold PROs |
|
|
Term
| 19. congenital disorders of glycosylation (CDGs) |
|
Definition
a. Impair N-linked glycosylation of PROs
b. Failure to glycosylate PRO can’t secrete PRO and impairs EC enzymatic reactions
c. Clinical Presentation
i. PRO losing enteropathy
ii. Hypoglycemia
iii. Hypotonia |
|
|
Term
| 20. Lysosomal Sulfatase deficiency |
|
Definition
| GAGs accumulate in lysosome |
|
|
Term
| 21. Scurvy, Ehlers Danlos, Osteogenesis Imperfectica |
|
Definition
a. Malfunction
i. Proline hydroxylation collagen |
|
|
Term
|
Definition
a. Deletion of CFTR1 gene
b. Interferes w/ PRO folding & glycosylation
c. Incorrect folding of CFTR protein cytosol for degradation |
|
|
Term
|
Definition
a. Transfer of Phosphate to mannose impaired
b. Lysosomal PRO don’t reach their compartment in the lysosome accumulation of PROs in lysosome
i. In fibroblast: detect dense inclusion bodies of non-fxn lysosome
ii. In serum: detect lysosomal PROs that didn’t reach destination |
|
|
Term
| 24. Deafness-dystonia Syndrome |
|
Definition
a. Mutation of TIM
b. Prevent assembly of fully fxn mito |
|
|
Term
|
Definition
i. Inappropriate MYC activation
ii. TRANSLOCATION OF CH’SOME 8 & 14
1. Moves MYC from ch’some 8 (normal) to ch’some 14 (mutation)
MYC on ch’some 8 Normal regulated
MYC on ch’some 14 Abnormal unregulated under control of immunoglobin (Ig) heavy chain promoters
B-cells continually produce Ig, now overproduce MYC uncontrolled cell proliferation |
|
|
Term
|
Definition
Colon carcinoma Familial adenomatous polyposis (FAP)
Regulate β-catenin (cell-cell signaling) |
|
|
Term
|
Definition
Many types Li-Fraumeni Syndrome
GF signal pathway
Regulates RAS activity |
|
|
Term
|
Definition
melanoma Familial Melanoma
Inhibit CDK4 & CDK6 |
|
|
Term
|
Definition
| retinoblastoma Familial Retinoblastoma Regulate G1 restriction point of cell cycle |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Breast Cancer Familial breast cancer DNA double strand break repair |
|
|
Term
|
Definition
| Skin Xerodoma Pigmentosa Nucleotide excision repair |
|
|
Term
|
Definition
| Leukemias & lymphomas Ataxia telangiectasia DNA double strand break signaling |
|
|
Term
|
Definition
Defective p53
Breast, colon cancer, soft tissue, brain, leukemia, adrenocortical cancers
Defective p53 binds normal p53 non-functional tetramer
P53Unable to stop cell cycle for DNA repair |
|
|
Term
|
Definition
p53Unable to stop cell cycle for DNA repair
p21 Unable to inhibit cell proliferation
RB Unable to inhibit cell proliferationE6 inhibits p53
E7 inhibits p53, p21, & RB
Cervical cancer
HPV produces E6 & E7 |
|
|
Term
|
Definition
Child inherits mutant RB1 gene
Germline mutation RB1 mut in ALL tissues
Somatic mutation in retinal cell
no functional Rb PRO produced
Both eyes affected; younger pts |
|
|
Term
FAP
(Familial Adenomatous Polyposis |
|
Definition
ONE Mutated APC gene (Adenomonatous Polyposis Coli)
*NOT Anaphase Promoting Complex (also apoptosis)
Defective cell division & aneuploidy
Mut APC…β-catenin unregulated Wnt binds β-catenin complex into nucleus & activates TXN of myc & cyclin D (G1-CDK4/6) cell proliferation
No Wnt signal….APC gene APC tumor suppressor tumor suppressor binds β-catenin degradation by proteasome
Wnt signal….Wnt binds β-catenin activate Myc & Cyclin D in nucleus cell proliferation |
|
|
Term
HNPCC
(Hereditary Non-Polyposis Colorectal Cancer)
(Lynch Sundrome) |
|
Definition
Mutated MLH1 or MLH2
Defective mismatch repair
Microsatellite instability
(microsatellites are short tandem repeats throughout genome…prone to replication errors that are normally repaired by mismatch repair enzymes ) |
|
|
Term
|
Definition
Philadelphia Ch’some
Reciprocal translocation b/t Ch9 & Ch22
Ch9 & Ch22 translocation BCR-ABL Fusion
ABL Tyr Kinase (normally reg. apop & signaling pathways)
BCR-ABL ABL constantly activates BCR cell proliferation
Imatinib mesylate (Gleevec) inhib BCR-ABL |
|
|
Term
| Non-small cell lung cancer |
|
Definition
Mutated EGF-R
Gefinitib Tyr Kinase Inhibitor |
|
|
Term
|
Definition
Overexpress HER2-R (ErbB2)
Herceptin (monoclonal antibiotic) accelerate HER2-R internalization |
|
|
Term
|
Definition
| Rituximab (monoclonal antibody) flag CD20 of B-cell for destruction |
|
|
Term
|
Definition
a. Tyrosine Kinase inhibitor
b. Inhibits BCR-ABL in CML |
|
|
Term
|
Definition
a. Tyr Kinase Inhibitor
b. Prevents EGF phosphorylation stops txn |
|
|
Term
|
Definition
a. (monoclonal antibiotic) accelerate HER2-R internalization
b. Reduces available
i. Reduces availability of receptor for dimerization activate Tyr Kinase domains instead |
|
|
Term
|
Definition
monoclonal antibiotic) accelerate HER2-R internalization
b. Reduces available
i. Reduces availability of receptor for dimerization activate Tyr Kinase domains instead |
|
|
Term
|
Definition
| a. Reverses DNA methylation and reactivate silenced genes |
|
|
Term
|
Definition
a. Mode of Inheritance
i. AR
b. Clinical features of PKU.
i. Phe –(Phe Hydroxylase / DHBtn Reductase) Tyr
[THBtn + O2 DHBtn + NADH THBtn +02 DHBtn + H20]
ii. Phe Hydroxylase primarily located in LIVER
iii. Excess Phe converted to phenylpyruvate (for disposal)
iv. Urine is high in phenylpyruvate
v. enzyme defects that cause PKU
1. Phe Hydroxylase
2. DHBtn Reductase
c. Treatment
i. Low Phe diet supplemented with Tyr
ii. Patients with PKUshould avoid aspartame (Nutrasweet)
a. Aspartame Asp + Phe + methanol
b. Patients with PKU accumulate phenylpyruvate which causes brain damage |
|
|
Term
|
Definition
d. Mode of Inheritance
i. AR
a. Clinical Features of Cystic Fibrosis
i. Incorrectly folded PROs cytoplasm for degradation
1. Deletion of CFTR1 gene
2. Interferes w/ PRO folding & glycosylation
3. Incorrect folding of CFTR protein cytosol for degradation
4. Loss of CFTR function
a. Cl- not transported, so Na+ & H2O won’t follow
b. Symptoms
i. accumulation of Thick mucus in lungs & GI tract
ii. respiratory infections
iii. pancreatic malfunction
iv. Congenital Absence of the Vas Deferens infertility in males
c. Diagnosis
i. chloride sweat test Sweat of patients is abnormally salty; test electric conductance of skin
ii. Allele Heterogenity (genotype/phenotype correlation) Pt might have different mutations on each mutant allele
1. Pancreatic Sufficient CFTR: Some patients have enough residual CFTR activity for normal digestion
2. Pancreatic Insufficient: Require pancreatic enzyme supplementation
iii. Modifier Genes
1. PROs don’t act alone, so activity of other PROs has impact on severity of CFTR mutations
iv. carriers may be less susceptible to cholera
b. Treatment of Cystic Fibrosis
i. Chest percussion to loosen mucus
ii. Bronchodilators to help clear mucus
iii. Antibiotics to prevent infection
iv. Admin pancreatic enzymes
v. Last Resort: Lung Transplant |
|
|
Term
| Neurofibromatosis Type I (NF1) |
|
Definition
i. Mode of Inheritance
1. AD
2. Complete penetrance
3. Variable expressivity – less than half of newborns show symptoms, b/c it’s an age dependent disease; don’t forget that genes have modifying affect in each other, thus affecting the expressivity of mutant genes
4. Pleiotropic: affects skin, iris, CNS
ii. Clinical Features
1. Mutated NF1 gene on ch’some 17
2. NF1 expressed in cytosol of neurons, schwann clls, oligodendrocytes, astrocytes, & leukocytes
3. Diagnosis
a. 6+ café au lait macules
b. Lisch nodules in iris
c. 2+ neurofibromas
d. 1+ plexiform neurofibromas (1 usually enough for Dx) |
|
|
Term
|
Definition
i. Mode of Inheritance
1. AD
2. CAG Triplet Expansion: insertion of an aa into the reading frame
a. Can occur during mitosis or meiosis
3. Complete penetrance
4. Demonstrates Anticipation
ii. Clinical Features
1. Multiple neurological disorders around age 40
a. Dementia
b. Uncontrolled movement of limbs
2. Late onset results in people having kids before they know they are carriers
3. Gain of function mutation
iii. Anticipation
1. CAG triplet expansion polyglutamine residues in PRO
a. Normal: 9-35 CAG repeats
b. HD disease: when exceed 40 CAG repeats
c. Premutation: 35 repeat higher chance of producing gametes w/ HD
d. See pg 563
i. Age of onset depends directly on #CAG repeats
2. Asymptomatic individual has 50% chance of passing on premutation
3. Chance of increasing size of expansion during mitosis and meiosis increase chance offspring inherit more aggressive mutation (early onset w/ stronger symptoms) |
|
|
Term
|
Definition
i. Mode of Inheritance
1. AD
2. New mutation in FGFR3 (fibroblast growth factor)
a. Mutation hotspots
ii. Clinical Features
1. FGFR3 is a Tyr Kinase receptor
a. Normally: FGF binds FGFR3 inhibits chondrocyte proliferation inhib bone growth
b. Mut FGFR3: constitutively ACTIVE inhib bone growth
2. Fitness = 0.2 (20% fertility)
3. Mutation Hotspot
a. Area in ch’some where mutations occur frequently
b. Typical hotspot:
i. CG dinucleotide repeat
ii. C often methylated methylcytosine
iii. Spontaneous deamination of methylcytosine yields T
iv. C for T (or G for A) substitutions occur at rate 25x greater than any other nucleotide exchange
c. Correlation b/t new mutations and paternal age
i. More mutations in older sperm than younger sperm
ii. |
|
|
Term
| 5. Osteogenesis Imperfectica Type I |
|
Definition
i. Mode of Inheritance
1. AD
2. Dominant negative effect
ii. Clinical Features
1. Null mutation of Type I collagen genes
a. Diagnosis is similar to Ehlers Danlos b/c genetics is diagnosis driven
2. Skeletal deformity
3. Predisposition to fractures |
|
|
Term
| 6. Familial Hypercholestremia |
|
Definition
i. Mode of Inheritance
1. AD
2. Gene Dosage Effect
a. Heterozygotes have 2x elevated serum cholesterol
b. Homozygotes have 4x elevated serum cholesterol
3. Mutated LDL receptor
ii. Clinical Features
LDL receptor = glycoprotein spanning plasma membrane
1. C-terminal – inside cell
2. N-terminal – outside cell
a. Recognizes
i. ApoB
ii. ApoE of LDL & VLDL
b. Binding leads to endocytosis of receptor and uptake of LDL & VLDL |
|
|
Term
| 7. Duchenne Muscular Dystrophy |
|
Definition
i. Mode of Inheritance
1. XR
2. Dytrophin is a large target for mutation
3. 2x mutation rate of other diseases due to its size
ii. Clinical Features
4. Defective dystrophin gene
5. Dystrophin links cytoskeleton to ECM
a. Dystrophin interacts w/ actin, syntrophins, & dystobrevin
b. Also binds β-dystroglycan (large transmembrane complex) interacts w/ α-dystroglycan on EC plasma membrane
c. α-dystroglycan links cell to α-laminin of ECM
d. see appendix 20d…..Draw pg 569
6. Lack of dystrophin muscles accumulate damage & disintegrate |
|
|
Term
| 8. Becker Muscular Dystrophy |
|
Definition
iii. ¬Mode of Inheritance
1. XR
2. Same as DMD
iv. Clinical features
3. Mutation does not completely abolish dystrophin function |
|
|
Term
| 9. Hypophosphatemic Rickets |
|
Definition
i. Mode of Inheritance
1. XD
ii. Clinical Features
1. Mut. PHEX gene
a. Low phosphate levels
b. Stunted bone growth
c. Short stature
d. Dental abnormalities
e. Low renal phosphate reabsorption |
|
|
Term
| 10. Incontinentia Pigmenti |
|
Definition
i. Mode of Inheritance
1. XD
2. Lethal in males (only 1 X Ch’some) – won’t see pedigree w/ males
ii. Clinical Features
1. Mutated IKK-gamma gene (NEMO)
2. skin lesions evolve through characteristic stages:
a. blistering (from birth to about four months of age),
b. a wart-like rash (for several months),
c. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
d. linear hypopigmentation.
3. Alopecia
4. hypodontia
5. abnormal tooth shape
6. hyperpigmentation
7. microencephaly |
|
|
Term
| Leber’s Hereditary Optical Neuropathy (LHON) |
|
Definition
i. Mode of Inheritance
8. Mito
ii. Clinical Features
9. Mutated ND1 gene
10. ND1 is part of complex I of ETS
11. Rapid deterioration of optic nerve blindness |
|
|
Term
|
Definition
AD Defect in bone growth New mutations
Fitness
Dominant negative allele
Mutation hotspot |
|
|
Term
| Becker Muscular Dystrophy |
|
Definition
XR Lack of dystrophin muscles accumulate damage & disintegrate
Same as DMD except Mutation does not completely abolish dystrophin function |
|
|
Term
|
Definition
AR Defective Cl- channel Allele heterogeneity
Modifier loci |
|
|
Term
| Duchenne Muscular Dystrophy |
|
Definition
XR Defect in distrophin New mutations
Large target |
|
|
Term
|
Definition
| AR & AD Collagen disorder |
|
|
Term
| Familial Hypercholesterolemia |
|
Definition
| AD Defective LDL receptor Allele heterogenity |
|
|
Term
|
Definition
|
|
Term
| Glycogen Storage Disorders |
|
Definition
AR Hypoglycemia
Accumulation of glycogen |
|
|
Term
|
Definition
| XR Sensitivity to H2O2 generating agents & fava beans |
|
|
Term
|
Definition
AD Neurological disorders New mutation
Triplet expansion
Anticipation |
|
|
Term
|
Definition
XD Mut. PHEX gene
Low phosphate levels
Stunted bone growth
Short stature
Dental abnormalities
Low renal phosphate
reabsorption |
|
|
Term
|
Definition
XD Skin Rashes
Alopecia
hypodontia
abnormal tooth shape
hyperpigmentation
microencephaly |
|
|
Term
| Leber’s Hereditary Optical Neuropathy |
|
Definition
| Mito Defect on mito. DNA Heteroplasmy |
|
|
Term
|
Definition
AD Multiple tumors New mutations
Variable expressivity
Pleiotropy |
|
|
Term
| Osteogenesis Imperfectica Type I |
|
Definition
AD Defective Type I collagen Dominant negative allele
Allele heterogeneity |
|
|
Term
|
Definition
| AR Tyr metabolism Newborn screening |
|
|
Term
|
Definition
AD Tumor on the retina Rb regulates G1 restriction point of cell cycle
2 Hit model
1. Germline RB1 gene mutation
2. somatic RB1 mutation in retinal cell |
|
|
Term
|
Definition
AR
Hemolysis Hemoglobinopathy
1. Substitution of Glu for Val in beta chain creates STICKY HYDROPHOBIC PATCH
2. In R-form patch is shielded
3. In T-form patch exposed hydrophobic effect causes T- form to polymerize into fibers that distort RBC
Treatment:
Hydroxyurea
1. stimulates expression of fetal copies of B-globin gene in adults compensates for defective copy of gene in adult |
|
|
Term
| Sucrase-Isomaltase Deficiency |
|
Definition
AR Sucrose/glucose polymer intolerance Sucrose Glucose + fructose
Disaccharides not cleaved cannot be taken up by the intestines osmotically active so influx of H2O into intestine diarrhea |
|
|
Term
|
Definition
46 XY Del(5p)
Symptoms:
Distinct cry
Distinct facial appearance
Microencephaly
Hypertelorism (eyes far apart)
Epicanthal folds
Low set ears
Microagnathia
Mental retardation
Heart defects |
|
|
Term
|
Definition
Neural crest migration anomaly
Del 22q11.2
Symptoms:
Structural or fxn defects of thymus
Heart defects (CGHF)
Reduced parathyroid fxn
Secondary hypocalcemia |
|
|
Term
| Velocardiofacial syndrome |
|
Definition
Symptoms:
Palatal abnormalities
Heart malformations
Facial characterizations
Narrow nasal root
Smooth philtrum
Developmental delays
Learning disability
Thymus malfunction |
|
|
Term
|
Definition
69XXX / 92XXXX
Cause:
fert by 2 sperm/ fert by 3 sperm |
|
|
Term
|
Definition
Down syndrome
Cause: non-disjunction of ch 21 during anaphase |
|
|
Term
|
Definition
Edward syndrome
Cause: non-disjunction of ch 18 during anaphase |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
a. Repress transcription
b. HDACs remove acetyl from histones chromatin condensation
c. Histone modification may be trigger for de novo methylation
d. Rett Syndrome
i. Defective MBPs
1. MBPs bind 5’ methylcytosine repress txn |
|
|
Term
| 14. Prader-Willi Syndrome |
|
Definition
i. Causes
1. Del 15q11-q13 on Paternal Ch 15 snoRNA region (maternal normally silences)
2. maternal disomy 2 Methylated maternal snoRNA on Ch 15
a. BOTH result in Lack of expression of snoRNAs
ii. Symptoms
1. Obesity
2. Excessive food seeking
3. Hypogonadism
4. Mental retardation |
|
|
Term
|
Definition
i. Causes
1. Del 15q11-q13 on Maternal Ch 15 UBE3A region (paternal normally silenced)
2. Paternal disomy 2 methylated paternal UBE3A on Ch 15
a. BOTH Lack of ubiquitin ligase (UBE3A) in brain
ii. Symptoms
1. Unusual face & movement
2. Seizures
3. Gait disorders |
|
|
Term
| 16. Beckwith-Wiedemann Syndrome (BWS) |
|
Definition
a. Paternal disomy Ch 11
b. Cause
i. Loss of methylation ( expression) of the same region of the maternal Ch11
c. Result
i. Overexpression of IC1 gene overabundance of IGF2 (insulin like growth factor)
d. Affect
i. Kidney
ii. Adrenal
iii. Liver problems |
|
|
Term
|
Definition
DNMT Inhibitor
i. Causes hypomethylation of genome
ii. Correct cancer caused by hypermethylation (of tumor suppressors) |
|
|
Term
|
Definition
| promote histone hyperacetylation (expression) and gene re-expression (acetylates oncogenes to restore normal function |
|
|
Term
| 20. Sporadic (mulitafactorial) |
|
Definition
a. Cleft lip, isolated anomaly
b. Low RR (recurrence risk) |
|
|
Term
|
Definition
a. Defective Robin Sequence is cause of cleft lip due to extrinsic constraint on embryo interfering with growth
b. Low RR
c. Small, receding jaw |
|
|
Term
| 22. Treacher-Collins Syndrome (TDS) |
|
Definition
a. AD
b. High risk of complications
c. RR= 50%
d. Characteristics
i. Small jaw
ii. Down-slanting palpebral fissures
iii. Malar hypoplasia |
|
|
Term
|
Definition
a. Mut. PAX6
i. Severity varies but can include
1. absence of eyes
2. craniofacial defects
3. CNS deformities
b. PAX6 is ‘master control’ gene assoc w/ devel of sensory organs |
|
|
Term
| 24. VACTERL (mesoderm defect) Wk 4 devel |
|
Definition
a. Vertebral
b. Anal atresia
c. Cardiac
d. Tracheo-esophageal fistula
e. Renal
f. Radial limb defects |
|
|
Term
| 26. Smith-Lemli-Optiz Syndrome (SLOS) |
|
Definition
i. AR
ii. Defective post-translational modification of SHH (inadequate cholesterol synth)
iii. Multiple severe congenital malformation |
|
|
Term
| 27. Polycystic Kidney Disease |
|
Definition
a. Mut. PKD1 or PKD2
i. Unable to sense fluid stream proliferation not stopped no cell polarization polycystic kidney disease |
|
|
Term
| 28. Lissencephaly (smooth brain) |
|
Definition
a. Mut. LIS1 (PAFAHB1)
i. Interferes w/ orderly migration
ii. Smooth, thickened cortex lacking defined cell layers |
|
|
Term
|
Definition
| Patient has testes & ovaries |
|
|
Term
| Male Pseudohermaphrodites |
|
Definition
Failure to develop male genitalia
Causes
Defective testes development during embryogenesis
Problem w/ androgen synth by testes (5-α-reductase)
Deficient androgen receptor production
androgen insensitivity
draw pg 640 |
|
|
Term
| Female Pseudohermaphrodites |
|
Definition
Normal ovaries
Ambiguous or male genitalia
Causes
Congenital Adrenal Hyperplasia (CAH)
Def 21-hydroxylase
Involved in cortisol synth
Draw pg 640 |
|
|
Term
|
Definition
i. Threshold of liability and Recurrence Risk
1. Males 1/200 males need less contributing alleles to be affected
a. Threshold of liability lower for males
b. Recurrence risk lower for males
2. Females 1/1000 higher threshold, so must have more contributing alleles to manifest disease than male females have higher risk of (RR) have affected siblings, ESPECIALLY a brother.
a. Threshold of liability higher for females
b. Recurrence Risk higher for females |
|
|
Term
| 30. Developmental Hip Dysplasia (DDH) |
|
Definition
i. Threshold of liability and recurrence risk
1. 1/1000 births
2. More common in females ~ 5-9 female for every 1 male
a. Threshold of liability is lower for females
b. Recurrence Risk higher if 1st affected child is male |
|
|
Term
| 31. Diginic Retinitis Pigmentosa |
|
Definition
i. Two factors
ii. Retinitis Pigmentosa 7 (Slow Onset)
1. Mut PRPH2 & Mut ROM1
2. Manifests as 2 heterozygous mutations, one in each gene
a. Note: AD in PRPH2 causes disease, but not ROM1 |
|
|
Term
|
Definition
i. Many factors
ii. Risk Factors
1. Older
2. Obese
3. Family history
4. History of gestational diabetes
5. Impaired glucose tolerance
6. Sedentary
7. Higher risk if African American, Hispanic, Native American, Pacific or Asian American
iii. 38 susceptible loci to T2D
1. Important bc patients in the future will bring in print outs from Direct To Consumer Genetics Companies wondering what it all means
iv. 26M (8.3%) in US have T2D
v. 19M diagnosed
vi. 7M undiagnosed |
|
|
Term
|
Definition
a. Unknown etiology
i. 12 year study Honein et al., 2000. Am. J Epidem. 152(7), 658-665
1. Parents w/ family history of clubfoot 6 times more likely to have affected child than parents w/o affected relatives
2. In families w/ history of clubfoot, maternal smoking increases risk of child having clubfoot 40%
3. Both risk factors combined 20 fold elevated risk
4. Conclusion
a. Clubfoot results from both environmental and genetic factors
b. Risk is higher when both factors are present than one alone
c. Must be an interaction b/t environmental and genetic factors |
|
|
Term
|
Definition
i. AD
ii. Prenatal Screening
1. Amniocentesis & chorionic villus sampling
2. Southern Blotting & PCR
a. CGT repeat in DM gene
iii. Symptoms
1. Muscle atrophy
2. Cataracts
3. Cardiac arrhythmias
4. Infertility
5. Endocrine disorders
6. Characteristic facial appearance |
|
|
Term
|
Definition
i. Inhibits vit K & vit K epoxide reductases
1. Polymorphism in detoxifying gene P450 PRO slow metabolism of warfarin higher sensitivity
2. Mut VKORC1 (vit K epoxide reductase) higher tolerance |
|
|
Term
|
Definition
a. Gold standard: Direct sequencing (microarray, PCR)
b. Most common CFTR mutation
i. ΔF508 (66%)
ii. Microarray assay (faster) or PCR (slower)
1. To detect known mutations
2. There is a list of top 10 mutations of CFTR |
|
|
Term
| 37. Duchenne Muscular Dystrophy (DMD) |
|
Definition
a. Mut dystrophin gene (largest gene in genome)
b. Large insertions and deletions of DMD
i. Southern Blotting or quantitative PCR
1. Best way to detect insertions and deletions
ii. No top 10 list
c. BMD |
|
|
Term
| 38. Monoclonal and Polyclonal antibody production |
|
Definition
a. Point mutation in DMD
b. Antibodies produced by B-lymphocytes in response to antigen
i. Each B-cell produces one type of antibody
ii. Antibodies bind the epitope (domain) of antigenic agent
iii. Polyclonal antibodies obtained by injecting animal w/ antigen
1. Immune system produces different antibodies against each epitope of the antigen
2. Collect blood
3. Antibodies in serum |
|
|
Term
| 39. Monoclonal antibodies |
|
Definition
a. B-lymphocytes produce antibodies against epitopes of antigen
b. Collect B-lymphocyte fraction from spleen and fuse w/ myeloma cell
c. Hybridoma cells produce antibodies
d. Select and grow hybrid cells making desired antibody |
|
|
Term
|
Definition
| Tumors and AIDS Stable (random insertion into genome) |
|
|
Term
|
Definition
| Cold, conjunctivitis, gastroenteritis No integration. Expression lost in 3-4 weeks |
|
|
Term
|
Definition
|
|
Term
| Herpes Simplex Virus (HSV-1) |
|
Definition
Mouth Ulcers, genital warts, encephalitis
Stable
Maintained outside ch’some |
|
|
Term
|
Definition
|
|
Term
| 41. Severe Combined Immunodeficiency Syndrome (SCIDS) |
|
Definition
1. Absent adenosine deaminase (ADA)
No ADA Deoxyadenosine accumulates converted to dATP High dATP levels TOXIC to rapidly dividing cells loss of lymphocytes
2. dATP inhibits ribonucleotide reductase (required for ribonucleotide triphosphate synthesis)
3. Treatment procedure
a. T-cells (B-lymphocytes) isolated from patient
b. Retrovirus transfers ADA gene into cells
c. Cells are selected and grown in culture
d. Re-implant into patient |
|
|
Term
|
Definition
i. Treat cells directly in patient
ii. Works best on epithelial cells
iii. Cystic Fibrosis
1. Mut CFTR gene
2. Treatment
a. Deliver functional copy of CFTR gene into lung epithelial cells
b. Uses adenovirus vector |
|
|
Term
| 43. Explain the basis for RNA interference (RNAi) |
|
Definition
a. RNAi shut down expression of undesirable genes
i. Viral genes
ii. Oncogenes
iii. Dominant mutant genes
b. Basis for treatment: Double stranded RNA molecules initiate destruction of certain mRNA molecules
Double stranded RNA (dsRNA) enzyme complex (DICER) small interfering RNA (siRNA) loaded onto RNA Induced Silencing Complex (RISC) catalyzes cleavage of mRNA w/ sequence homologous to siRNA |
|
|
Term
|
Definition
a. (monoclonal antibiotic) accelerate HER2-R (ErBB2) internalization
b. Reduces availability of EGF receptor ERBB2 (HER2) for dimerization activate Tyr Kinase domains instead
c. INHIBITS CELL PROLIFERATION |
|
|
Term
| 45. Leber Congenital Amaurosis (LCA) |
|
Definition
a. AR
b. Multifactorial disorder
c. Mut RPE65 gene
i. Cant generate retinal pigment for light detection
d. Severe retinal dystrophy
i. Nystagmus
ii. Poor vision
iii. Poor pupillary response
iv. Franschettis oculo-digital sign (eye poking/ pressing & rubbing)
e. Treatment
i. In vivo injection of Adenovirus vector w/ functional RPE65 gene sub-retinally
ii. Gene expression takes place enzyme restored |
|
|
