Diseases Exam 1 Flashcards
Transthyretin amyloidosis
caused by transthyretin misfolding in old age. affects heart, kidneys, and respiratory tract
AL amyloidosis
caused by Ig light chain misfolding due to plasma cell dyscrasias (abnormalities). Affects are systemic, sometimes with local foci (excluding brain)
AA amyloidosis
caused by serum amyloid A protein overproduction in chronic inflammation, leading to amyloid formation in the spleen and elsewhere
Dialysis-associated amyloidosis
caused by hemodialysis (blood cleaning) leading to amyloid formation in the bones and joints. β2- micro globulin is a surface protein involved in immune responses that can detach from cells and deposit in bones and joints, causing arthritis.
type 2 diabetes mellitus
one possible cause is oversecretion of islet amyloid protein (secreted with insulin in the vesicles) leading to amyloid accumulation in and around the pancreatic islents
Frontotemporal dementia
age related or inherited mutation leading to accumulation of tau protein in the brain. Tau protein stabilizes microtubules in axons and is regulated by phosphorylation and dephosphorylation. Excessive phosphorylation can lead to diseases including Alzheimers and frontotemporal dementia.
Parkinson’s disease
α-synuclein- unstably folded membrane protein that can aggregate into granules called Lewy bodies, found in dopaminergic neurons in most patients with Parkinson’s. Increased production of α-synuclein or abnormal α-synuclein protein can lead to early onset Parkinson’s
Alzheimer Disease
can be inherited, or related to age or down syndrome. related to β-amyloid precursor protein accumulation causing amyloid plaques. Tau protein stabilizes microtubules in axons and is regulated by phosphorylation and dephosphorylation. Excessive phosphorylation can lead to diseases including Alzheimers and frontotemporal dementia.
Prion Diseases
Prion protein is a normal nervous system protein bound to glycosylphosphatidylinositol with a flexible N-terminus that can vary in conformations. It extremely rarely refolds, but can cause normal prion proteins to refold into the abnormal conformation and form aggregates leading to neuron death. The excessive neuron death leads to holes in the brain, which resembles a sponge upon death (hence the term spongiform encephalopathy). This progression describes Creutzfeldt-Jakob disease where someone inherits a mutant prion gene (single AA mutation) or from exposure. There is also a variant form of the disease (vCJD) where it is transmitted from infected cattle, as well as kuru, which is transmitted by cannibalizing an infected individual.
Anemia
defined as Hb below the normal range of 12%-17%. This can be due to an impairment in Hb synthesis, a condition called microcytic hypochromic anemia, usually caused by an Fe deficiency. Can also be genetic like in thalassemia where the synthesis of Hb α and β chains is disrupted.
Methemoglobinemia
a condition where iron is oxidized from the ferrous to the ferric state, so it cannot transport oxygen. Normally methemoglobin (oxidized Hb) is present at 1% concentration due to the activity of methemoglobin reductase, but a deficiency in this enzyme leads to congenital methemoglobinemia. This condition is treated with methylene blue, a dye that is reduced to leucomethylene blue, which then reduces the ferric iron back to ferrous iron.
CO poisoning
- due to 200x affinity for Hb of CO than O2 called competitive antagonism. CO binding also increases O2 affinity of the other subunits, so decreases oxygen delivery. Normal nonsmokers have 2% CO-Hb, but each pack of cigarettes increases this by 2.5%. Hookah smoke is especially high in CO and can cause acute CO poisoning, also seen in car-related suicide attempts. 70% is fatal
Niemann-Pick Disease
lipid storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. The original description of NPD referred to what is currently termed NPD type A, which is a fatal disorder of early childhood characterized by failure to thrive, hepatosplenomegaly, and a rapidly progressive neurodegenerative course that leads to death by age 2-3 years.
Tay-Sachs
caused by Hexosamindase A deficiency and leads to accumulation of gangliosides in neurons
systemic lupus erythematosus (SLE)
the presence of high titer of antibodies to histones is diagnostic for systemic lupus erythematosus (SLE)
Rett Syndrome
severe neurological disease in females due to mutation in methyl-cytosine binding protein 2 (MeCP2), which represses transcription when bound to methyl cytosine in DNA. Very rare to be passed on between generations, 99% is due to de novo (spontaneous mutations; increases with advanced PATERNAL age). Begins at 1-2 years of age and leads to loss of motor and cognitive skills, seizures, autism, repetitive movements and death between 12 and 40 years.
Huntington’s Disease
Some microsatellite DNA occurs in regulatory sequences. In Huntington’s disease, a 3 NT CAG repeat normally repeated 6-34 times (codes for polyglutamine tract in protein huntingtin) is repeated >36 times, causing protein to form clusters that kill cells in the basal ganglia. The greater the expansion, the easier the onset of disease
Leber’s hereditary optic neuropathy (LHON)
mutation in mitochondrial DNA @ bp 11778 that affects complex I of ETC (NADH dehydrogenase) and disables leads to disabilities in areas where aerobic respiration is essential (like optic nerve)
Zellweger syndrome
deficiency in any of the 12 PEX genes leading to dysfunctional peroxisomes. Leads to accumulation of VLCFAs and BCFAs in the blood and insufficiency in plasmologen synthesis leading to brain and respiratory problems . Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts. Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.
beriberi
vitamin B1 deficiency (thiamin)
pellagra
vitamin B3 deficiency leading to dermatitis, dementia, and diarrhea
Xeroderma pigmentosum (XP)
affected individuals have deficiencies in NER complex; show dry skin (xeroderma) and freckles (pigmentosum) in sun-exposed areas and are extremely sensitive to UV radiation
Cockayne syndrome
deficiency in ERCC6 and/or 8 (aka CsB and/or CsA); leads to photosensitivity (not to extent of XP), delayed neurological development, and premature aging.
Aneuploidy
abnormal # of chromoromes
turners syndrome
(45, XO)
Kleinfelder
XXY
Philadelphia chromosomes
part of 9 and 22 exchange places and the fusion causes leukemia due to the formation of a constitutively active fusion protein
familial hypercholesterolemia
autosomal dominant disease; people who are homozygous can have heart attacks and deaths as early as 30. Most often caused by mutation in LDLR which removed LDL from blood
sickle cell disease
Autosomal recessive disease that results in sickle shaped RBCs due to mutation in Hb that causes polymerization
X-SCID
X-linked recessive disease. Severe combined immunodeficiency
Fragile X-syndrome
- causes intelectual disability; most common mental retardation in males and can cause retardation in females. Symptoms include elongated face, protruding ears, heart problems, skin problems, etc (pleiotropy) inherited in fashion that is very close to X-linked dominant and some females are less affected due to X inactivation
- Caused by trinucleotide repeat expansion (CGG) on. FMR1 gene. Fragile X gene is a subunit of the RNA-induced silencing complex (RISC); disease though to be due to incomplete silencing of specific mRNAs. Normally between 5-40. >200 causes fragile X. In between leads to “premutation” that leads to some manifestation of disease, but not full diagnosis.
- In women with premutation, gene can expand in gametogenesis. Doesn’t occur in males, can only pass on premutation for reasons unknown
- Anticipation- tends to happen with trinucleotide repeat disorders. Means that symptoms begin to show at earlier age and severity is greater with each passing generation. e.g. most often in neurological trinucleotide repeat diseases fragile X and Huntington’s disease.
ataxia telangiectasia
Deficiency in ATM leads to ataxia telangiectasia (defects in nervous and immune systems and high incidence of cancer)
Duchenne muscular dystrophy (DMD)
caused by a mutation in the dystrophin gene, which codes for a protein that is involved in stabilization of the plasma membrane to the cytoskeleton and participates in calcium handling. This gene is the largest human gene known (2.5 million bp long) and has 79 exons. DMD causes wheelchair confinement by age 12 and death by respiratory failure within 10 years of onset. 2/3 of mutations are large deletions; half of which are in frame. When the deletion is out of frame it gives clinical DMD, when it is in frame, it gives a less severe form of the disease (Becker muscular dystrophy- BMD)
Retinis pigmentosa
disease due to mutation of rhodopsin which results in night blindness due to apoptosis of photoreceptors due to UPR as a response to the number of misfolded rhodopsin proteins
Gaucher’s disease
defficiency in glucocerebrosidase leading to an accumulation of glucocerebroside and increased lysosome size
I-cell disease
deficiency in M-6-P tagging of lysosome enzymes, leading to excretion of lysosomal enzymes
Cholera
cholera toxin is endocytose into the cell and ADP ribosylates the αs (stimulatory) subunit; inactivates the GTPase activity of the α rendering it permanently active and causing an increase in cAMP. This continuously activates the cystic fibrosis channel (CFTR) causing a big entry of chloride ions and water that follows, causing extreme water loss and dehydration
Prader-Wili syndrome
dysfunctional copy of 15q 11-13 received from father; maternal imprinting; father’s copy is the one normally expressed, but if it is mutated, causes hyperphagia, obesity, intellectual disability, hypotonia, and hypogonadism
Angleman syndrome
dysfunctional copy of 15q 11-13 received from mother; Paternal imprinting; mother’s copy is the one expressed. Leads to inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability
Whooping cough
aka pertussis; caused by pertussis toxin. Toxin is endocytosed and ribosylates the αi subunit (inhibitory subunit) resulting in the protein being locked in the GDP bound state, resulting in increased cAMP
