Tweakage 1
Tweakage 2
Mini Tweakege
Progeria 1
Progeria 2
100
Point for each answer:
How many MAIN types of Glycogen Storage Disease are there? (extra points if you can name them all)
What is Type 1 called?
What is deficient in Type 1?
100
What is the inheritance pattern most commonly seen in vW Disease?
What are the clinical signs?
What about the clinical presentation in Hemophillia A that you would not see in vW Disease?
Autosomal Dominant (75% of the time)
Heavy bleeding (menstrual), poor wound clotting, fatigue, normal appetite, frequent nosebleeds, pale conjunctiva/ mucous membranes, Regular Rate and Rhythym
Hemophillia A will have hemarthroses (bleeding into the joints)
100
What would happen to some of the lab values in patients with Hereditary Spherocytosis? In relation to:
1.MCHC 2.MCV 3.Hb 4.HCT 5.RDW 6.Reticulocytes
VERY elevated MCHC
Usually normal MCV
Low HB
Low HCT
Elevated RDW
Elevated Reticulocytes
100
What are the risk factors of HPS? What is the likelihood of your child being born with this condition if you already have a child with this condition?
There are no known factors, such as lifestyle or environmental issues, which increase the risk of having progeria or of giving birth to a child with progeria. Progeria is extremely rare. For parents who have had one child with progeria, the chances of having a second child with progeria are about 2 to 3 percent.
100
Name at least 4 visual symptoms of HPS
- Slowed growth, with below-average height and weight
- Narrowed face, small lower jaw, thin lips and beaked nose
- Head disproportionately large for the face
- Prominent eyes and incomplete closure of the eyelids
- Hair loss, including eyelashes and eyebrows
- Thinning, spotty, wrinkled skin
- Visible veins
- High-pitched voice
200
Points for each answer:
What is the inheritance pattern for Familial Hypercholesteremia?
What gene is impaired in FH?
What kind of mutation is it? What does this gene code for?
Autosomal Dominant
PCSK9 gene
Gain of function mutation reduces the levels of LDL receptors at the cell surface below normal, leading to increased blood cholesterol
200
What is the drug used to treat CML? What is this drugs MOA, Adverse effects?
Imatinib
MOA: inhibits Bcr-Abl tyrosine kinase → blocks proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as in fresh leukemic cells in Philadelphia chromosome positive CML
AE: fluid retention → ankle and periorbital edema may develop
200
Where is vWF stored?
What is one specific test you can use to dx it?
vWF is stored in endothelial cells and megakaryocytes
Von Willebrand Ristocetin Cofactor assay measures the ability of a plasma sample to agglutinate platelets in the presence of the antibiotic Ristocetin
200
What is the typical cause of death for pts with HPS?
atheresclerosis
200
A mutation in what gene causes HPS? What protein does this code for?
LMNA gene, Lamin A protein
Mechanistically, HGPS is underpinned by a single heterozygous C-to-T mutation at position 1824 of the LMNA gene, which results in the accumulation of an aberrant farnesylated form of lamin A called progerin in the inner nuclear membrane
300
What is the inheritence pattern for sickle cell disease? What is the mutation?
What is seen on an x-ray?
What clinical presentation do pts experience that cause them usualy to become treated?
Autosomal Recessive Disease; Missense mutation (glutamic acid to valine) on the 6th chromosome
Hair-on-end presentation on x-ray (expansion of medullary cavities in skull)
Vaso-occlusive crisis (lots of pain)
300
Describe the three phases of Chronic Myelogenous Leukemia? What clinical presentation is associated with each phase?
Chronic phase: Mostly asymptomatic. When symptomatic, features include: Weight loss, fever, night sweats, fatigue. Splenomegaly → abdominal discomfort in the left upper quadrant
Accelerated Phase: Erythrocytopenia → anemia. Neutropenia → infection and fever. Infarctions (splenic and myocardial infarctions). Extreme pleocytosis. Retinal vessel occlusion. Leukemic priapism. Terminal phase: myelofibrosis Extreme splenomegaly → palpable in lower left quadrant or pelvic cavity
Blast Phase: Symptoms resemble those of acute leukemia. Rapid progression of bone marrow failure → pancytopenia and bone pain. Severe malaise
300
What virus do you have to be wary of in hereditary spherocytosis? What about this MOA makes it so you have to be wary of it in relation to this disease?
Parvovirus B19; due to replicating in the bone marrow and inhibiting erythropoesis for ~2 weeks. Spherocyte turnover is a few days.
300
What health problems do not increase with HPS?
Other health problems frequently associated with aging — such as arthritis, cataracts and increased cancer risk — typically do not develop as part of the course of progeria.
300
Name at least 4 pathological signs and symptoms of HPS?
- Severe progressive heart and blood vessel (cardiovascular) disease
- Hardening and tightening of skin on the trunk and extremities (similar to scleroderma)
- Delayed and abnormal tooth formation
- Some hearing loss
- Loss of fat under the skin and loss of muscle mass
- Skeletal abnormalities and fragile bones
- Stiff joints
- Hip dislocation
- Insulin resistance
400
DAILY DOUBLE
List at least 3 proteins that are impaired in Hereditary Spherocytosis?
What are some treatment options for HS?
Lifelong Folic acid supplementation for any hemolytic anemia
Splenectomy (so that RBC don’t get trapped in spleen) + Vaccination against S pneumonia and H influenzae (to give body support to fight certain infections now that they don’t have a spleen)
EPO: To produce more RBC’s
400
What is the inheritance pattern for Factor V Leiden?
What is the DNA Mutation? What does this mutation inhibit?
Autosomal Dominant
A DNA point mutation substitutes guanine for adenine → corresponding mRNA codon forms glutamine in place of arginine on position 506 (Arg506Gln mutation) near the polypeptide cleavage site of factor V
In such patients, Gln506-Va is resistant to cleavage by aPC (activated protein C) → factor V remains active → activates prothrombin → becomes thrombin → increases thrombotic events
400
DAILY DOUBLE
Examples of 4 Treatment options thats can be used for Factor 5 Leiden? What are the MOAs of these treatments?
Heparin: (3 types) indirect thrombin inhibitor, induced antithrombin 3 to inhibit factor Xa
Warfarin: Inhibits vitamin k epoxide redeuctase
Dabigatran: Direct Thrombin Inhibitor
Rivaroxaban: Factor Xa inhibitor
400
What is the function of Lamin A
This protein plays an important role in determining the shape of the nucleus within cells. It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus
400
What is the life expectancy of someone with progeria?
The average life expectancy of a person with progeria is 14.5 years. However, some children die as young as 6 years old, and some adults with progeria live into their early 20s.
500
What is the mutation seen in cutaneous melanoma? What does this lead to?
What is ABCDE? Describe the ABCDE of a typical melanoma?
BRAF V600E mutation -> activates MAPK which then activates ERK -> enhanced cell proliferation
ABCDE - asymmetrical, irregular borders, color variation (typically brown/black, can be white/blue), larger diameter (6mm+), Evolution of a mole Pruritic Can have elevated borders
500
What are the differences between right sided and left sided colon carcinoma?
What mass precursors can eventually lead to cancer?
Left Sided: Changes in bowel habits, Colicky abdominal pain (due to obstruction), Gross Patho: mostly infiltrating mass
Right Sided: Occult bleeding or melena Manifestations of iron deficiency anemia (due to chronic bleeding) Gross Patho: mostly exophytic mass (originates from the liver)
Adenomatous polyps are benign growths from the inner lining of the colon into the lumen. In some cases, cancer can start here
500
What are the 2 treatment options for Cutaneous Melanoma?
Are they ever given in conjunction?
Dabrafenib or Vemurafenib - BRAF kinase inhibitor - treats metastatic melanoma
Trametinib- MEK inhibitor
Using this combo inhibits the MAPK/ERK pathway
500
Describe the structural changes of the skin associated with aging and progeria in relation to HA and collagen
Hyaluronic acid
Naturally produced in the body, clear gooey substance. Largest amounts found in skin, connective tissue, and eyes .May be due to the lack of integrity of the nucleus that may then effect the connective tissue. Aging process and exposure to sun can decrease amounts on the skin
Collagen keeps cartilage elasticity, while HA holds moisture HA runs short, cells can no longer hold enough water and collagen itself degenerates leading to loss of skin elasticity
500
What brand new treatment recently got approved for HGPS? What is it's MOA?
lonafarnib; Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin; as progerin farnesylation is important for localization to the nuclear membrane, lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients