All Case Studies Flashcards
Maple Syrup Urine Disease
Failure to metabolize certain AA–> Val, Ile, Leu
Urine tested positive for keto acids and had elevated levels of branched amino acids
Val,Ile,Leu –> a-keto acids –> acetyl coA der. Leu
*last step doesn’t happen when you have this disease
Treatment: should stop intake of nourishment involving high levels of Val, Ile, Leu
Cystic Fibrosis
High levels of IRT- immunoreactive Trypsinogen (normally produced by the pancreas)
Mutations can change amino acids resulting in changes in protein length, charge, etc –> chloride channels get messed up
Impaired Cl channels leads to enhanced Na absorption –> volume of liquid that sits on the surface is reduced –> mucus becomes more viscous –> bacterial growth
Typhoid Fever
Treated with ciprofloxacin type of Quinolone
-binds to DNA gyrase (topo II) and inhibits its ligase domains leading to DNA fragmentation
Only works on gram + and - bacteria, so does not affect humans
HIV/Shingles
Nucleoside analogs resemble the nucleosides so much that they can incorporate in the DNA- however they quickly lose functionality (lack of -OH on 3’ prevents additional nucleotide additions
Cannot participate in replication, transcription, etc.
Myotonic dystrophy
Autosomal dominant trinucleotide (CTG repeat) disorder in which the more repeated elements causes increased severity
Shows anticipation: age onset of disease gets earlier and earlier and severity increases with successive generations
Having repeats in the genome when not needed cause RNA to become too long –> interfere with proteins in some way
Aicardi-Goutieres Syndrome
Autosomal encephalopathy with microcephaly, calcifying basal ganglia, etc
result of defects with RNaseH2 gene that makes RNaseH (degrades RNA/DNA hybrids and removes RNA primers)
B/c RNA primers left in DNA, transcription is faulty and replication worsens it –> many mutated proteins
Caused by mutations in genes that are required for the Pre-RC complex (OriC1, 4, 6, CDC 6) –> impaired replication results in failure to grow
Dyskeratosis Congenita
Causes low blood count b/c of bone marrow failure –> caused by telomere maintenance malfunction by a mutated telomerase and shows anticipation as well (worsens with successive generations)
Constitutional mismatch repair deficiency, Xeroderma Pigmentosum
Characterized by defects in DNA repair, especially vulnerable to the sun and therefore get many skin cancers easily
XP genes can be knocked out, so can’t repaid any of the pyrimidine dimers that form –> get cancer from the mutated DNA
Pitt-Hopkins Syndrome
See episodes of hyperventilation and apnea, sunken eyes, prominent high nasal bridge
Caused by inability of transcription factors to bind to DNA b/c of mutations in the basic regions of the transcription factors (less + charge, less binding to DNA, low transcription rate)
Rett Syndrome
Caused by MeCP2 on the X Chromosome
Mutated MeCP2 unable to properly bind to methylated DNA and block transcription, so see high rates of gene expression where there shouldn’t be
Cutaneous T-cell lymphoma
Chromatin remodeling errors resulted in lymphoma by overactive HDAC and less expressed HAT –> DNA is less acetylated and tumor supressor genes are more expressed, stopping cancer
Fabry Disease
Lysosomal storage disease where there is a lack of glycosidase A
Amino acid mutation in alpha glycosidase A results in it being misfolded in the ER and globosides begin to accumulate in lysosomes and results in inflammation
Treatment: target the misfolded proteins and used specific small molecule chaperones to try and fix the problem
Progeria
Results from nuclear lamin defect in which farnesyl groups are attached to type A lamins and then attached to nuclear envelope
Mis-shapen nuclei cause inhibition of import to FG Nup that forms the basket of the nuclear pore –> difficulty moving proteins into the nucleus due to nonfunctional pores
