Exam 02 Disease/Disorders Flashcards
1
Q
Cockayne Syndrome
A
- rare AR congenital disorder mutant genes ERCC6 (type B) and ERCC8 (type A) proteins involved in TCR of DNA
- if DNA not repaired cell dysfunction and death occur
- developmental delay
- photosensativity
- progeria (premature aging)
- hearing loss and eye abnormalities
- death by first 2 decades of life
- type B 70% cases
2
Q
BRCA mutations in breast cancer
A
- homologous recombination repair disruption
- BRCA1 and BRCA2 are tumor suppressor genes
- mutations cause 5 fold increase in women’s risk of breast/ovarian cancer before menopause and also increase men’s risk of breast cancer
- BRCA1= higher risk cervical/uterine/pancreatic/colon cancer in women and pancreatic/testicular/prostate in men
- BRCA2= increase risk of developing melanoma and pancreatic/gallbladder/bile duct cancer in women
3
Q
Xeroderma Pigmentosum (XP)
A
- problem with NER complex
- skin is sensitive to sunlight and prone to melanomas/squamous cell carcinoma
- UV light causes thymidine dimers to form in DNA
- dimers normally easily repaired in normal people by NER
- people with XP proteins (XP-a or XP-G) in the NER complex exhibit disease
4
Q
Heredity colon cancer
A
- inherited mutations in 1 of the alleles of genes in MER complex (MSH2/MSH1) increase susceptibility to colorectal cancers
- an aquired mutation in remaining GOOD copy of gene would render MER system nonfunctional and allow tumor development
5
Q
Generally what is a porphyria?
A
- inherited metabolic disorders
- purple pigment
- caused by defects in heme synthesis
- different types depending on which enzyme is defective
6
Q
Acute Intermittent porphyria
A
- defective enzyme= PBG (porphobilinogen) deaminase (liver)
- AD
- deficiency leads to excess production of ALA and PBG
- periodic attacks of abdominal pain and neurologic dysfunction
**hepatic (Neurologic symptoms)
7
Q
Congenital Erythropoietic porphyria
A
- defective enzyme= uroporphyrinogen III synthase (erythrocytes)
- AR
- deficiency leads to accumulation of uroporphyrinogen I and its red-colored, air oxidation product uropophyrin I
- photosensativity red color urine and teeth, hemolytic anemia
*erythropoietic= skin, photosensitivity
8
Q
Porphyria cutanea tarda (PCT)
A
- defective enzyme= uroporphyrinogen decarboxylase
- AD
- deficiency leads to accumulation of uroporphyrinogen III
- most common porphyria in USA
- photosensitivity resulting in vesicles and bullae on skin of exposed area
- wine red colored urine
*hepatoerythropoietic
9
Q
Variegate porphyria
A
- defective enzyme= protoporphyrinogen oxidase
- AD
- photosensitivity and neurologic symptoms and developmental delay in kids
*hepatic
10
Q
What is jaundice generally?
A
- hyperbilirubinemia
- elevated levels of BR in blood stream
- normal levels= unconjugated–> 0.2-0.9 and conjugated–> 0.1-0.3
- imbalance between production and excretion of bilirubin
- pre-hepatic
- Intra-hepatic
- post-hepatic
11
Q
Pre-hepatic jaundice
A
- increased production of unconjugated BR
- excess hemolysis
- hemorrhage
- capacity of liver to uptake/conjugate/excrete BR exceeded
- ex) G6P dehydrogenase deficiency
- neonatal jaundice due to problems with maternal-fetal blood group incompatibility
12
Q
Pre-hepatic jaundice findings:
A
- elevated blood levels of unconjugated or direct BR
- normal levels conjugated BR
- normal AST and ALT
- urobilinogen in urine(b/c capacity of liver to conjugate and excrete BR not impaired)
- direct BR absent in urine
13
Q
Intra-hepatic jaundice
A
- impaired hepatic uptake, conjugation or secretion of conjugated BR
- generalized hepatic dysfunction due to:
1. Liver cirrhosis
2. Viral hepatitis
3. Criggler-Najaf syndrome
4. Gilbert syndrome
14
Q
Intra-hepatic jaundice findings:
A
- variable increases in unconjugated and conjugated BR
- increase ALT and AST
- urobilinogen levels urine normal
- conjugated BR detected in urine
15
Q
Post-hepatic jaundice
A
- problems with BR excretion
- aka cholestasis (decreased bile flow)
- caused by:
1. Obstruction to biliary drainage
2. Cholangiocarcinoma
3. Gall stones
4. Infiltrative liver disease
5. Lesions
6. Drugs
16
Q
Post-hepatic jaundice findings:
A
- elevated blood levels of conjugated BR
- small increase in unconjugated BR
- normal AST and ALT
- elevated ALP and bile salts
- conjugated BR in urine (dark)
- no urobilinogen in urine
- no stercovalinagine in feces (pale stool)
17
Q
Neonatal jaundice
A
- newborns develop jaundice due to elevation of un-conjugated bilirubin
- physiological jaundice
- 2 contributing factors:
1. Breakdown fetal Hb as replaced by adult Hb
2. Immature hepatic metabolic pathways unable to conjugate/excrete BR
3. Deficiency of UDP-GT enzyme
*accumulation of excess BR in blood leads to jaundice symptoms
18
Q
What is phototherapy
A
- BR changes conformation to form more soluble isomer when exposed to blue fluorescent light
- used to treat jaundice in newborns
19
Q
What is hepatitis
A
- inflammation of the liver
- leads to liver dysfunction
- causes: viral infection, alcoholic cirrhosis, liver cancer
- increased levels of unconjugated and conjugated BR in blood
- BR accumulated in skin and sclera causing yellow discoloration
- dark urine
20
Q
Megaloblastic Macrocytic Anemia
A
- large erythrocytes (with normal Hb content relation to size)
- caused by either Vit B12 or Folate deficiency (find out by Schiling test)
- occurs as a result of diminished synthesis of DNA in developing RBC in bone marrow
- B12 deficiency= then cannot de-methylate N5-methyl-THF to renter folic acid cycle as THF and give carbons for nucleotide synthesis (folate stuck as 5N-methyl-THF)
21
Q
Fragile X mental retardation
A
- disruption in FMR1 gene which encodes protein for neurological function
- over 200 copies of CGG repeat (more susceptible to methylation of cytosine)
- methylation extends to promoter region and transcription is turned off
- FMR1 gene becomes silent
22
Q
2 examples of locus of heterogeneity
Individual with same phenotype but different genotypes
A
- CF (AR)
2. Osteogenesis Imperfecta= mutation in collagen genes charm 7 and 17
23
Q
2 examples of variable expressivity
Individuals with same genotype with multiple phenotypes
A
- PKU
- Neurofibromatosis= skin patches vary in size/shape
(Have disease, just different severities, affect different organ systems)
24
Q
Example of AR disorder
A
- tyrosinase-negative albinism
- AR= skips generations
- affects meals and females
25
Example of X-linked recessive disorder
- duchennes muscular dystrophy
| - no male carriers
26
Example of X linked dominant disorder
- hypophosphatemia= abnormally low levels of phosphorus in blood--> defective kidney reabsorption
- rare no carriers
27
Example of reduced penetrance
- retinoblastoma (90% of individuals inheriting the disease display the phenotype)
- AD???
