Biochem Flashcards
Orotic aciduria
Inability to convert orotic acid –> UMP (pyrimidine synthesis)
Sx: Inc orotic acid in urine megaloblastic anemia (does NOT improve w/ B12) NO hyperammonemia (vs. OTC)
Adenosine deaminase deficiency
AR
Accumulation of adenosine, ATP, dATP
dATP inhibits Ribonucleotide reductase –> inhibits DNA synthesis –> dysfxn T & B-cells
SCID
SELF-MUTILATION
Gout
Choreoathetosis
Retardation
Lesch-Nyan syndrome
- HGPRT deficiency
- Guanine & hypoxanthine can’t –> GMP & IMP = Gets degraded to uric acid –> hyperuricemia
- Excess IMP & GMP –> excess purines –> CNS damage
Nucleotide excision repair defect
Xeroderm pigmentosum
Mutation of DNA mismatch repair
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
- AD
- recognizes UNmethylated new strand mismatches
- 80% –> CRC
- PROXIMAL colon alway involved
Cerebellar (ataxia)
Spider angiomas
IgA deficiency
Ataxia telangiectasia
- ATM gene - DNA repair enzymes
alpha-amantin
Inhibits RNA Pol II (mRNA)
Found in death cap mushrooms –> liver failure
Aminoglycosides
Bind 30S
Inhibits formation of initiation –> misread mRNA
Chloramphenicol
Inhibits 50S peptidyl transferase
Macrolides
Binds 50S –> Blocks translocation
Clindamycin & Chloramphenicol block?
Peptide bond formation
Tetracyclines
Bind 30S
Prevent aminoacyl-tRNA synthetase attachment
I-Cell Disease
Inherited lysosomal storage disorder
Failure to + Mannose-6-Phosphate –> secrete enzymes vs. –> lysosome
Sx:
Coarse facial features
Clouded corneas
Restricted joints
Fatal in childhood
Pyogenic infections - staph, strep
Albinism
Peripheral neuropathy
Chediak-Higashi Syndrome
- Failure of phagosome & lysosome fusion
- Defect Lysosomal Regulator Trafficking gene (LYST) = microtubule polymerization
- AR
Kartagener’s Syndrome
Dynein arm defect (retro –> -)
Immoble cilia
Infertility
Bronchiectasis
Recurrent sinusitis
Assoc w/ situs inversus
Oubain
Inhibits binding to K+ site –> inhibits Na/K pump
Cardiac glycoside MOA
Inhibit Na/K pump –> inhibits Na/Ca exchange –> Inc Ca –> Inc contractility
Scurvy
Lack of Vit C
Required for hydroxylation of collagen w/ proline or lysine
Type I collagen defect
Osteogenesis imperfecta
Type I = AD
Type II = Fatal
Type I collagen (glycosylation)
- Multiple fx
- Blue sclera
- Hearing loss
- Dental imperfections
Type III Collagen defect
Ehlers-Danlos
Type III collagen defect (cross-linking)
- Hyperextensible joints
- Easy bruising
- Berry anyuerysms
- Hyper mobile joints/dislocation
Basket-weave GBM, Type IV collagen defect
Alport syndrome
- Deafness
- Nephritis
- Ocular disturbances
Defect in Fibrillin
Marfan’s Syndrome
- Tall w/ long extremities
- Pectus excavatum
- Long, tapering fingers & toes (Arachnodactyly)
- Medial necrosis of aorta –> dissecting AAs & aortic insufficiency
- Floppy mitral valve
- Subluxation of lens
Locus heterogeneity w/ MEN 2B, homocystinuria
alpha-1 anti-trypsin deficiency
Misfolded protein aggregates in heptocyte ER –> cirrhosis
PAS + globules in liver
Dec elastic tissu in lungs –> PANACINAR emphysema
Codominant trait
Southern Blot
DNA
Southwestern Blot
DNA-binding proteins (transcription factors)
Microarray
Level of gene expression
ELISA
Ag-Ab reactivity
FISH
Localization of genes & visualize anomalies
Fluorescence = gene present
Incomplete penetrance
Not everyone w/ mutation shows sx
Pleiotropy
1 gene >1 effect
PKU
Loss of heterogeneity
Mutation in tumor suppressor gene - complimentary allele must be deleted –> cancer
Mosaicism
Cells in body differ d/t POST-fertilization loss of genetic material
germ-line –> disease not in parent’s cells
Hyperphagia, hypogonadism, hypotonia, Paternal deletion
Prader-Willi
- should be active
Maternal in inactivated
Seizures, ataxia, inappropriate laughter “happy puppet,” maternal deletion
Angleman Syndrome
- should be active
Paternal inactive
AR trait
1 generation
2-carrier parents
XR trait
No male-to-male
More severe in males
Sons of heterozygous mothers = 50%
XD trait
ALL females of affected father
Both MF affected
FGFR3 mutation
Achondroplasia
- enchondral ossification
Dwarfism
Short limbs
NORMAL trunk & head
Normal lifespan & fertility
Assoc w/ advanced paternal age
AD & sporadic
AD Polycystic Kidney Disease
Adults
BILATERAL MASSIVE kidneys
PKD1 - Chr16
Polycystic liver
Berry aneurysm
MVP
AR Polycystic Kidney Disease
Infantile
Congenital hepatic fibrosis & Liver cysts
Portal HTN
HTN
Familial Adenomatous Polyposis
APC gene - chr5 (5 letters in polyp)
Polyps after puberty –> cancer
Familial hypercholesterolinemia
Defect/absent LDL receptor –> inc LDL
Achilles tendon xanthomas
Severe atherosclerosis –>MI b4 20
Osler-Weber-Rendu (Herediatry telangiectasia)
Telangiectasias
Recurrent epistaxis
Skin discolorations
AVMs
Hereditary spherocytosis
Spectrin or Ankyrin defect
Inc MCHC
Cure = splenectomy
Huntington
CAG expansion
Chr4 (hunting 4 food)
caudate atrophy –> dec GABA & Ach
Choreiform movements, progressive dementia
Multiple endocrine neoplasias (MEN) gene mutation
MEN 2A/B - RET gene
Lisch-nodules
Cafe-au-lait
Neural tumors
Scoliosis
Neurofibromatosis Type I
B/L Acoustic schwannoma
Juvenile cataracts
Neurofibromatosis Type II
NF2 gene - chr22
2 ears - NF2 - Chr22
Facial acne, hypopigmented lesion mainly on trunk, Hammartomas, Renal angiomyolipomas, Cardiac rhabdomyomas
Tuberous sclerosis
- adenoma sebaceum
- “ash leaf” spots
- Inc astrocytomas
B/L renal cell carcinomas
Hemangioblastomas of retina, cerebellum, medulla
Von Hippel-Lindau Disease
- VHL gene on Chr3p