Diseases for MCM Flashcards
BRCA 1
Usually carries out DNA repair pathways, tumor suppressant
mutuation or damage creates improper folding of BRCA protein –> not useful
patients predisposed to beat, ovarian cancer.
This protein has a-Helix
Huntingtons disease
DNA mutation leads to long (>36 glutamine residue)
Translated to long protein
Protein builds up and interferes with nerve function
Notice drop in neurotransmitter levels (GABA)
Characterized by ‘boxcar’ basal ganglia
Barth Syndrom
Defect in metabolism of phospholipids
Mutated TAZ gene = nonfunctional tafazz protein (which modifies lipid in mitochondrial membrane –> low cardiolipin (mito membrane lipid)
patients suffer from: exercise intolerance, growth delay, neutropenia, cardiomyopathy, and reduced life expectancy
Progeria
Advanced aging syndrome
Cells express low levels/ no telomerase
Telomerase role in cancer
Telomerase has high levels of telomerase
Cells continue to divide, live for ever
Bloom’s Syndrome
Deffective BLM protein (RecQ helicase)
Unable to unzip DNA for repair (predisposed to cancer)
Pateints show: premature aging, photosensitivity, red facial ‘butterfly-like’ rash, short stature, developmental defects.
Blooming butterfly
Thalassemia
inherited blood disorder. Body makes abnormal Hb
one point mutation can throw off splicing mechanism
Trisomy 21
Down syndrome (extra copy of chromosome 21)
Usually from nondisjunction of oocyte formation
Growth retardation, mental disabilities
craniofacial defects
cardiac defects in 40%, usually septal defects of PDA
Trisomy 18
Edward Syndrom (extra chromosome 18)
Only 5-10 % survive first year, handful live to be 10
Clenched fists: fingers/ hands flexion
Cardiac defects, mental disability, craniofacial: low-set ears
Trisomy 13
Patau Syndrome (extra chromosome 13)
Mental disability, cardiac defects, craniofacial: cleft lip and palate, eye defects
Deafness
90% die within first month, 5% live past first year
Klinefelter Syndrome
Trisomy– XXY, 47
presence of Barr bodies (inactive male x chromosome)
Sterile
Testicular atrophy, gynecomastia (develop breasts)
Usually very tall, long limbed
Triple X syndrome
Females, XXX, 47
Two barr bodies (inactive X chromosome) in cells
carrying degree of mental disability
amenorrheic
No classical pattern of malformation
Monosomy
Turner Syndrome 45, X
One less copy of X chromosome, female
Paternal nondisjunction, 80%
Only monosomy compatible with life
Short, broad chest, short neck
congenital lymphedema of hands/feet
Streak gonads
Lack of secondary sex characteristic development at puberty
Cri du Chat syndrome
partial deletion of the short arm of chromosome 5
characteristic cry of the cat due to malformation of larynx
growth retardation
Mental Disability, microcephaly
Cardiac defects
Deletion 4q Syndrome
Partial deletion of long arm of chromosome 4
Growth retardation,
varying degrees of mental disability
Cleft palate
Limb abnormalities
Angelman Syndrome
Microdeletion- long arm of MATERNAL chromosome 15
Intellectual disability
puppet-like gait
Absent Speech
Prone to unprovoked periods of uncontrolled laughter
Prader-Willi Syndrome
Micro deletion- long arm of PATERNAL chromosome 15
Intellectual disability
obesity and hypotonia
Hypogonadism
Undescended testes
von Gierke disease
deficient G-6 phosphotase, GSD type I
cannot release glucose from G6P
Severe hypoglycemia, lactic acidosis, hepatomegaly (due to increase in g6P), hyperuricemia
Hyperlipidemia is secondary– body realizes it needs another form of energy, breaks down lipids and dumps in blood.
Glycogen storage disease
Pyruvate Kinase deficiency
won’t make sufficient ATP because no pyruvate
Can cause hemolytic anemia
build up of 2,3 BPG—> decreases affinity for O2
Hemolytic anemia
PK deficiency= No Heinz bodies
G6PD= Heinz bodies
Retinal Blastoma
Bad Rb gene > can’t stop EIIF from turning on replication genes.
Rb is a tumor supressant
eye cancer
ALS
Characterized by?
Amyotrophic Lateral Sclerosis, thought to be cause by protein aggregates
Characterized by progressive degeneration of motor neurons.
Occurs in brainstem, brain and spinal cord
2 proteins thought to form aggregates
- Superoxide dismutase (SOD I)- handles superoxide free radicals from mitochondria. Free radicals build up cause stress for cell and ER > cell death
- TDP 43- Part of transcription process. Recruited when pre mRNA is going to be processed. Form occlusion granules in motor neuron and glial cells
Mechanisms:
- Aggregates inhibit Autoplagy and Ubiquitin proteosome sysetms.
- disturbance is RNA metabolism
- effect communication between neurons
- cytoskeletal defects, axonial transport dysfunction
- mitochondrial dysfunction
Causes muscle atrophy of skeletal musces
Type II diabetes (related to protein misfolding)
insulin resistance, loss of B cell function and mass
protein: Amylin (IAAP)- hormone co-localized, co-secreted, co-packaged with insulin.
Misfolded Amylin- causes dysfunction in b cells (decrease mass) ER stress (hyperglycemia, insulin compensation...) > misfolded protein> defective folding response, defective ubiquitin... > inhibition of protein synthesis > aggregates (only takes hours or days to aggregate)
Also clogs up golgi> secretory vessels not working properly > Autophagy not working > proteins can form pores in mitochondria > trigger cell death
Amylin seems to bind to macrophages, cause inflammation
what does amylin do?
- inhibit glucagon
- delay gastric emptying
- tells brain that you are full
- cosecretion with insulin
related to type II diabetes, misfolded protein
misfolded protein can form pores in mitochondria.
Lactate Dehydrogenase deficiency
Patients cannot do moderate levels of exercise. Unable to use glycolysis to form ATP under anaerobic conditions. Because not regenerating NAD
Thiamine Deficiency with alcoholics (Wernicke-Korsakoff Disease)
Alcoholics are deficient in Thiamine
If no thiamine–> PDH does not work
Causes weakness, hypoglycemia, low ATP
DO not give i/v with glucose > will saturate system get turned to lactate > die of lactic acidosis
Ataxia (loss of control of bodily movements)
cerebral hemorrhage
memory loss
arsinic
found in rat poison, pesticides, chemicals, moonshine
inhibits PDH
Lactase deficiency
1 genetic condition of all time
symptoms- diarrhea, bloating, cramping
From osmotic and bacteria fermentation effects
Galactokinase deficiency
Cataracts early in life
Galactosemia
Related to either Glactokinase or G16 uridyl transferase deficiency
Glactokinase not as sever (only cataracts early)
Gal 1P uridyl transferase deficiency
Galactosemia, more severe version
Early cataracts AND other symptom(s): vomitting diarrhea after lactose ingestion lethargy liver damage, hyperbillirubinemia Mental retardation
depends on which tissues it builds up in.
More serious because Gal1P is tagged and can’t leave the cell, brings water in and causes damage
Fuctokinase deficiency
Benign
Aldolase B deficiency
Symptoms: Lethargy, vomitting Liver damage, hyperbillirubinemia Hypoglycemia Hyperuracemia renal proximal tubule defects
No brain damage here
No early cataracts
Why is aldolase B deficiency noticed when babies start eating solids?
Because milk has lactose which is not effected in fructose metabolism. once starts solids the baby will intake sucrose and see problems.
Barbiturates, Rotenone
Rotenone is fish poison
Inhibit e- transfer from complex 1 to coenzyme Q
Cant make ATP in normal way. Bypass reactions, e- from other source to CoQ, still makes little ATP
Where and how does cyanide, carbon monoxide, and azide effect ATP production?
Cyanide binds to Fe3+ in Complex 4. Fe3+ cannot accept e to become Fe2+. This stops e flow and backs everything up.
No e flow= no H+ gradient = no ATP
Cyanide kills because no ATP is produced.
Treated by nitrite.
Where does Myxothiazol inhibit?
inhibits transfer from CoQ (UQH2) to complex 3
Where does oligomycin inbhibit?
(antibiotic) inhibits ATP synthase by binding to channel, blocking H+
Side effect of antibiotic
Pompe Disease
GSD type II
Lysosomal a14 glucosidase
cardiomegaly, muscle weakness, death by age 2
Cori Disease
GSD type III
Glycogen debranching and glycogen phosphorylase
Mild hypoglycemia, liver enlargment
Like type I but not as severe hypoglycemia
Anderson Disease
GSD type IV
Deficient branching enzyme
Liver failure causes death by age 2, immune system attacks liver, needs liver transplant
McArdle Disease
GSD type V
Deficient: Muscle glycogen phosphorylase
muscle cramps and weakness with exercise
McAdle for muscle
Hers Disease
GSD type VI
Glycogen phosphorylase deficiency
Hepatomegaly (like type I but more mild)
Hers for Hepatic
Wernicke-Korsakoff Disease
HMP Shunt pathway, genetic mutation in gene that makes transketolase
Transketolase has reduced affinity for TPP (thiamine pyrophosphate) THIAMINE is not deficient
PATH: ataxia, psychosis, confusion, brain not function properly
helped with thiamine therapy
G6PD deficiency
3 main features:
- immunodeficieny
- heinz bodies
- hemolytic anemia
G6PD makes pentose phosphates in liver and NADPH which is needed:
Liver: for biosynthesis (fatty acids, cholesterol, nucleotides)
Neutrophils: need e-s to kill bacteria via superoxides.
Erythrocytes: metHb reductase uses NADH to reduce metHb to Hb (detoxify free radicals)
Beriberi
Thiamine deficiency affecting all 4 thiamine dependent enzymes.
Situs inversus
Organs on opposite side (Complete, or Incomplete - one organ flipped)
Could be due to:
Improper signaling during gastrulation, failure to establish L-R six
Possibly due to cilia in node directing the wrong way.
20% patients develop chronic sinusitis which is why they think this is a cilia problem
Sirenomelia (Caudal dysgenesis)
Mermaid syndrome
Failure of mesoderm production in caudal portion of embryo
lower limb hypoplasia, fusion of limbs, vertebral anomalies, renal agencies, imperforate anus, genital anomalies
Teratoma
tumor of germ cell origin in other places
Kartagener Syndrome
primary cilliary dyskinesia
Microtubules can’t work/move. Can effect men or women.
Hydatidiform Mole
Complete mole- fertilization of an empty oocyte. Male pronucleus replicates to form diploid cell which divides.
Partial mole- poorly developed embryo, always triploid (XXX)
Secrete high levels of hCG
Persistent trophoblastic diesease- if mole not removed it can become invasive, 5% moles form caner
Amnion Problems
oligohydramnios- too little fluid (
