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334 Cards in this Set
- Front
- Back
Glycogen Storage Disease
1. Severe fasting hypoglycemia, increase glycogen in the liver, increase blood lactate.... 2. Deficient enzyme? |
1. Type I (von Gierke's)
2. G-6-P |
|
Glycogen Storage Disease
1. Cardiomegaly and early death (2 yrs) 2. Deficient enzyme? |
1. Type II (Pompe's)
2. Lysosomal alpha-1,4 glucosidase (acid maltase) |
|
Glycogen Storage Disease
1. MILD hypoglycemia with normal blood lactate levels 2. Deficient enzyme? |
1. Type III (Cori's)
2. (Debranching enzyme) alpha 1,6-glucosidase |
|
Glycogen Storage Disease
1. Increased glycogen in muscles, leads to painful cramps with exercise 2. Deficient enzyme? |
1. Type V (McArdle's)
2. glycogen phosphorylase |
|
Glycogen Storage Disease
1. Type I (von Gierke's) 2. Deficient enzyme? |
1. Severe fasting hypoglycemia, increase glycogen in the liver, increase blood lactate....
2. G-6-P |
|
Glycogen Storage Disease
1. Type II (Pompe's) 2. Deficient enzyme? |
1. Cardiomegaly and early death (2 yrs)
2. Lysosomal alpha-1,4 glucosidase (acid maltase) |
|
Glycogen Storage Disease
1. Type III (Cori's) 2. Deficient enzyme? |
1. MILD hypoglycemia with normal blood lactate levels
2. (Debranching enzyme) alpha 1,6-glucosidase |
|
Glycogen Storage Disease
1. Type V (McArdle's) 2. Deficient enzyme? |
1. Increased glycogen in muscles, leads to painful cramps with exercise
2. glycogen phosphorylase |
|
Lysosomal Disease
1. Peripheral neuropathy, cadio/renal disease (X-linked) 2. 2. Deficient enzyme? |
1. Fabry's Disease
2. alpha-galatosidase |
|
Lysosomal Disease
1. Hepatosplenomegaly, aseptic necrosis of the femur, (macrophages look like?) 2. 2. Deficient enzyme? |
1. Gaucher's disease
2. Beta-glucucerebrosidase |
|
Lysosomal Disease
1. Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on the macula, foam cells 2. 2. Deficient enzyme? |
1. Niemman-Pick
2. Sphingomyelinase |
|
Lysosomal Disease
1. Progressive neurodegeneration, NO hepatosplenomegaly, cherry-red spot on the macula, lysosomes have onion skin 2. 2. Deficient enzyme? |
1. Tay-Sachs disease
2. Hexosaminidase A |
|
Lysosomal Disease
1. central and peripheral demyelination 2. 2. Deficient enzyme? |
1. Metachromatic leukodystrophy
2. Arylsulfatase A |
|
Mucopolysaccharidosis
1. Aggressive behavior w/o cloudy corneal 2. gargoylism w/ cloudy corneal |
1. Hurler's
2. Hunter's |
|
Octamer subunits consist primarily of
|
lysine & arginine
|
|
Condensed, transcriptionally INACTIVE sterically inaccessible
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Heterochromatin
|
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Less condensed, transcriptionally ACTIVE, sterically accessible
|
Euchromatin
|
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Purines
|
A, G
|
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Pyrimidines
|
C, T, U
|
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Deamination of cytosine makes
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Uracil
|
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The bonds between G-C
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3 hydrogen bonds
|
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The bonds between A-T
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2 hydrogen bonds
|
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Amino acids that are necessary for purine synthesis
|
Glycine
Aspartate Glutamine |
|
base + ribose
|
Nucleoside
|
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base + ribose + phosphate; linked by 3'-5' phosphodiester bond
|
Nucleotides
|
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Pyrimidine are made from...,w/PRPP added later
|
Orotate precursor
|
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Accumulation of carbamoyl phosphate, which is then converted to orotic acid
|
Ornithine transcarbamylase deficiency
|
|
Findings:
- increased orotic acid in urine, megaloblastic anemia - does not improve w/ B12 or folic acid - No hyperammonemia and normal BUN |
Orotic aciduria
|
|
- autosomal recessive
- inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) - due to defect in orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase |
Orotic aciduria
|
|
Treatment for Orotic aciduria
|
Oral uridine administration
|
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Excess ATP and dATP imbalances nucleotide pool via feedback inhibition o f ribonucleotide reductase -> prevents DNA synthesis and thus decrease lymphocyte counts
|
Adenosine deaminase
|
|
- Defective purine salvage owing to absence HGPRT
- excess uric acid production |
Lesch-Nyhan syndrome
|
|
Converts hypoxanthine to IMP and guanine to GMP
|
HGPRT
|
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Lesch-Nyhan syndrome findings
|
- self-mutilation
- aggression - gout - hyperuricemia - retardation - choreoathetosis |
|
Target of allopurinol
|
Xanthine oxidase
|
|
Mutations in DNA/RNA
- Same aa, often base change in 3rd position of codon (tRNA wobble) |
Silent mutation
|
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Mutations in DNA/RNA
- Changed aa (conservative- new aa is similar in chemical structure) |
Missense mutation
|
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Mutations in DNA/RNA
- Change resulting in early STOP codon |
Nonsense mutation
|
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Mutations in DNA/RNA
- Change resulting in misreading of all nucleotides downstream, usually resulting in a truncated. nonfunctional protein |
Frame shift
|
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DNA replication
- particular sequence in genome where DNA replication begins - single in prokaryotes; multiple in eukaryotes |
Origin of replication
|
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DNA replication
- Y-shaped region along DNA template where leading and lagging strands are synthesized |
Replication fork
|
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DNA replication
- Unwinds DNA template at replication fork |
Helicase
|
|
DNA replication
- prevents strands from reannealing |
Single-strand binding proteins (SSBRs)
|
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DNA replication
- Creates nicks in the helix to relieve supercoils created during replication |
DNA Topoisomerases
|
|
DNA replication
- Makes RNA primer on which DNA polymerase III can initiate replication |
Primase
|
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DNA replication
- Elongates leading strand be adding deoxynucleotides to the 3' end - Elongates lagging strand until it reaches primer of preceding fragment - 3'-5' exonuclease proofreads each added nucleotide - only in Prokaryotes |
DNA polymerase III
|
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DNA replication
- Degrades RNA prime and fills in the gap with DNA - Prokaryotes only |
DNA polymerase I
|
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DNA replication
- Seals Okazaki fragment together |
DNA ligases
|
|
- Specific endonuclease release the oligonucleotide-containing damaged bases
- DNA polymerase and ligase fill and reseal the gap, respectively |
Nucleotide excision repair
|
|
- Specidil glycosylase recongnize and remove damaged bases
- AP endonuclease cuts DNA at apyrimidinic site - empty sugar is removed and the gap is filled and sealed |
Base excision repair
|
|
- Unmethylated, newly synthesized string is recognized, mismatched nucleotides are removed, and the gap is filled and resealed
|
Mismatched repair
|
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Part of cell cycle?
- Nucleotide excision repair |
G1
|
|
Part of cell cycle?
- Base excision repair |
G1
|
|
Part of cell cycle?
- Mismatch repair |
G2
|
|
hMLH1, hMSH2
Lynch Syndrome dna repair |
Mismatch repair
|
|
Xeroderma pigmentosum defect
|
Nucleotide excision repair defect prevents repair of thymine dimer
|
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Types of RNA
- most abundant |
rRNA
|
|
Types of RNA
- longest type |
mRNA
|
|
Types of RNA
- smallest type |
tRNA
|
|
Types of RNA
- rRNA |
link amino acid to proteins
|
|
Types of RNA
- mRNA |
carries information for protein synthesis
|
|
Types of RNA
- tRNA |
brings in correct amino acid
|
|
mRNA start codon
|
AUG (sometimes GUG)
|
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mRNA start codon in Eukaryotes
|
codes for methionine, which maybe removed before translation is completed
|
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mRNA start codon Prokaryotes
|
codes for formyl-methionine (f-Met)
|
|
Stop codons
|
UGA- "you go away"
UAA- "you are away" UAG- "you are gone" |
|
Site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus (AT-rich upstream with TATA and CAAT boxes)
|
Promoter region
|
|
Mutation commonly results in dramatic decrease in amount of gene transcribed
|
Promoter region mutation
|
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Stretch of DNA that alters gene expression by binding transcription factors
|
Enhancer region
|
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Site where negative regulator (repressors) bind
|
Silencer
|
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Enhancers and silencers may be located close to, far from, or even within (in an intron) the gene whose expression it regulates
|
Enhancers and/or silencers
|
|
Eukaryotes polymerase
- makes rRNA |
RNA polymerase I
|
|
Eukaryotes polymerase
- makes mRNA |
RNA polymerase II
|
|
Eukaryotes polymerase
- makes tRNA |
RNA polymerase III
|
|
- Found in death cap mushrooms
- inhibits RNA polymerase II - causes liver failure if ingested |
alpha-amanitin
|
|
alpha-amanitin
|
- Found in death cap mushrooms
- inhibits RNA polymerase II - causes liver failure if ingested |
|
Contain the actual genetic information coding for protein
|
Exons
|
|
Are intervening noncoding segments of DNA
|
Introns
|
|
Tumor suppressors
|
Rb and p53
|
|
Cell cycle stage of tumor suppressors (Rb and p53)
|
G1 to S
|
|
Cell types
- remain in G0, regenerate from stem cells |
Permanent
-neurons, skeletal and cardiac muscle, RBCs |
|
Cell types
- enter G1 from G0 when stimulated |
Stable (quiescent)
-hepatocytes, lymphocytes |
|
Cell types
- never go into G0, divide rapidly with a short G1 |
Labile
- bone marrow, gut epithelium, skin, hair follicles |
|
Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins; Nissl bodies
|
Rough Endoplasmic reticulum (RER)
|
|
Unattached to any membrane; site of synthesis of cytosolic and organellar proteins
|
Free ribosomes
|
|
Sire of steroid synthesis and detoxification of drugs and poisons
|
Smooth Endoplasmic Reticulum (SER)
|
|
Golgi apparatus
- retrograde; Golgi -> ER |
COP I
|
|
Golgi apparatus
- anterograde RER -> cis-Golgi |
COP II
|
|
Golgi apparatus
- trans-Golgi -> lysosomes, plasma membrane -> endosomes (receptor-mediated endocytosis) |
Clathrin
|
|
- inherited lysosomal storage disorder
- result in coarse facial features, clouded corneas, restricted joints movement (vs. Hurler's) - failure of addition of mannose-6-phosphate to lysosomal proteins |
I-cell disease (Inclusion cell disease)
|
|
Molecular motor proteins- transport cellular cargo toward opposite ends of microtubule tracks.
-anterograde? |
Kinesin
|
|
Molecular motor proteins- transport cellular cargo toward opposite ends of microtubule tracks.
-retrograde? |
Dynein
|
|
Chediak-Higashi syndrome
|
-microtubule polymerization defect
- resulting in decreased phagocytosis - recurrent pyogenic infections, partial albinism - peripheral neuropathy |
|
Kartagener's syndrome
|
- immotile cilia due to a dynein arm defect
- loud right heart sounds - result in male and female infertility - bronchiectasis and recurrent sinusitis |
|
Immunohistochemical stains
- Connective tissue |
Vimentin
|
|
Immunohistochemical stains
- Muscle |
Desmin
|
|
Immunohistochemical stains
- Epithelial cells |
Cytokeratin
|
|
Immunohistochemical stains
- Neuroglia |
GFAP (glial fibrillary acid proteins)
|
|
Immunohistochemical stains
- Neurons |
Neurofilaments
|
|
Drugs that act on microtubules
|
- Mebendazole/thiabendazole
- Griseofulvin - Vincristine/vinblastine - Paclitaxel - Colchicine |
|
Collagen
- Bone, Skin, Tendon, dentin, fascia, cornea, late would repair |
Type I
|
|
Collagen
- Cartilage (including hyaline), vitreous body, nucleus pulposus |
Type II
|
|
Collagen
- skin, BLOOD VESSELS, uterus, fetal tissue, granulation tissue |
Type III
|
|
Collagen
- Basement membrane or basal lamina |
Type IV
|
|
Ehlers-Danlos syndrome
|
Faulty collagen synthesis causing
- Hyperextensible skin - Tendency to bleed (easy bruising) - Hypermobile joints - dislocations, berry aneurysms, organ rupture |
|
Collagen affected in Ehlers-Danlos
|
Type III collagen defect
|
|
Osteogenesis imperfecta
|
Genetic bone disorder (brittle bone disease)
- autosomal dominant - Type I collagen defect - Multiple fractures - Blue sclerae (translucent CT over the choroid) - hearing loss - dental imperfections due to lack of dentin |
|
Alport's syndrome
|
- abnormal type IV collagen
- progressive hereditary nephritis and deafness - associated w/ocular disturbances |
|
Elastin
|
- Stretchy protein within lungs, large arteries, elastic ligament, vocal cords, ligamenta flava (spine)
- rich in glycine and proline -tropoelastin w/fibrillin scaffolding |
|
Inhibits breakdown elastase
|
alpha-1-antitrypsin
|
|
Defect in fibrillin
|
Marfan's syndrome
|
|
Molecular biology laboratory procedure used to amplify a desired fragment of DNA
|
Polymerase chain reaction (PCR)
|
|
Blotting procedure for a DNA sample
|
Southern blot
|
|
Blotting procedure for a RNA sample
|
Northern blot
|
|
Blotting procedure for a protein sample
|
Western blot
|
|
Genetic terms
-Definition: Neither of 2 alleles is dominant |
Codominance
|
|
Genetic terms
-Definition: Nature and severity of phenotype vary from 1 individual to another |
Variable expression
|
|
Genetic terms
-Definition: Not all individuals w/mutant genotype show the mutant phenotype |
Incomplete penetrance
|
|
Genetic terms
-Definition: 1 gene has more than 1 effect on individual's phenotype |
Pleiotropy
|
|
Genetic terms
-Definition: Differences in phenotype depend on whether the mutation is of maternal or paternal origin |
Imprinting
|
|
Genetic terms
-Definition: Severity of disease worsens or age of onset is earlier in succeeding generation |
Anticipation
|
|
Genetic terms
-Definition: If a Pt inherits or develops a mutation is a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops; Not true of oncogenes |
Loss of heterozygosity
|
|
Genetic terms
-Definition: exerts a dominant effect. Heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning |
Dominant negative muation
|
|
Genetic terms
-Definition: tendency for certain alleles at 2 links loci to occur together more often than expected by chance. Measured in a population, not in a family, and often varies in different populations |
Linkage disequilibrium
|
|
Genetic terms
-Definition: occurs when cell in the body have different genetic makeup -can be a germ-line; which may produce disease that is not carried by parent's somatic cells |
Mosaicism
|
|
Genetic terms
-Definition: Mutation at different loci can produce that same phenotype |
Locus heterogeneity
|
|
Genetic terms
-Definition: presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease |
Heteroplasmy
|
|
Genetic terms
-Definition: offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parents |
Uniparental disomy
|
|
Genetic terms
-Example: Blood groups (A, B, AB) |
Codominance
|
|
Genetic terms
-Example: Two Pts w/NF type 1 may gave varying disease severity |
Variable expression
|
|
Genetic terms
-Example: PKU cause many seemingly unrelated symptoms ranging from mental retardation to hair/skin changes |
Pleiotropy
|
|
Genetic terms
-Example: Prader-Willi and Angelman's syndromes |
Imprinting
|
|
Genetic terms
-Example: Huntington's disease |
Anticipation
|
|
Genetic terms
-Example: Retinoblastoma |
Loss of heterozygosity
|
|
Genetic terms
-Example: Mutation of Tx factor in its allosteric site. Nonfunctioning mutant can still bind DNA preventing wild-type Tx factor from binding |
Dominant negative mutation
|
|
Genetic terms
-Example: Lyonization- random X inactivation in females |
Mosaicism
|
|
Genetic terms
-Example: Marfan's syndrome, MEN 2B, and homocystinuria; all cause marfanoid habitus |
Locus heterogeneity
|
|
Hardy-Weinberg population genetics
- law assumes |
- no mutation occurring at the locus
- no selection for any of the genotypes at the locus - completely random mating - no migration |
|
Hardy-Weinberg population genetics
- disease prevalence formula |
p^2 + 2pq + q^2= 1
|
|
Hardy-Weinberg population genetics
- allele prevalence formula |
p + q= 1
|
|
Hardy-Weinberg population genetics
- heterozygote prevalence formula |
2pq
|
|
At a single locus, only 1 allele is active; the other is inactive (inactivated by methylation). Deletion of the active allele -> disease
|
Imprinting
|
|
Prader-Willi syndrome (genetic defect)
|
Deletion/inactivation of normally active Paternal allele (on chromosome 15)
|
|
Angelman's syndrome (genetic defect)
|
Deletion/inactivation of normally active Maternal allele (on chromosome 15)
|
|
Deletion/inactivation of normally active Maternal allele (on chromosome 15)
|
Angelman's syndrome
|
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Deletion/inactivation of normally active Paternal allele (on chromosome 15)
|
Prader-Willi syndrome
|
|
Prader-Willi syndrome (clinical presentation)
|
- obesity
- hypogonadism - hyperphagia - hypotonia - mental retardation |
|
Angelman's syndrome (clinical presentation)
|
- seizures
- inappropriate laughter - "happy puppet" - ataxia - mental retardation |
|
Modes of inheritance
- often due to defects in structural genes - Many generations - both male and females affected - often pleiotropic - in many case, presents clinically after puberty - family history crucial to diagnosis |
Autosomal Dominant
|
|
Modes of inheritance
- often due to enzyme deficiencies - seen in only generation - 25% of offspring from 2 carrier parents are affected - commonly more severe that dominant disorders - Pts often present in childhood |
Autosomal Recessive
|
|
Modes of inheritance
- sons of heterozygous mothers have a 50% chance of being affected - no male-to-male transmission - more severe in males - heterozygous females may be affected |
X-linked recessive
|
|
Modes of inheritance
- Transmitted through both parents - 50% of affect mother affected (both male/female) - ALL females offspring of affect father will be affected - Hypophosphatemic rickets (vit D resistant rickets) |
X-link dominant
|
|
Modes of inheritance
- transmitted only through mother - all offspring of affected female may show signs of disease - variable expression in population due to heteroplasmy |
Mitochondrial inheritance
|
|
Autosomal-dominant diseases
|
- achondroplasia
- ADPKD - familial adenomatous polyposis - familial hypercholesterolemia (hyperlipidemia type IIA) - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) - Hereditary spherocytosis - Hunting disease - Marfan syndrome - Multiple endocrine neoplasia (MEN 1,2A,2B) - Neurofibromatosis type 1 (von Recklinghausen's) - Neurofibromatosis type 2 - Tuberous sclerosis - von Hippel-Lindau diease |
|
Autosomal-dominant disease
- defect of fibroblast growth factor (FGF) receptor 3 - associated w/advanced paternal age - dwarfism; short limbs, but head and trunk normal |
- achondroplasia
|
|
Autosomal-dominant disease
- always bilateral - Pts w/ flank pain, hematuria, HTN, progressive renal failure - mutation in APKD1 (Chromosome 16) - associate w/ berry aneurysms & mitral valve prolase |
- ADPKD
|
|
Autosomal-dominant disease
- deletion on chromosome 5 (APC gene) - progresses to cancer unless resected |
- familial adenomatous polyposis
|
|
Autosomal-dominant disease
- Elevated LDL, defect/absent LDL receptor - severe atherosclerotc disease - tendon xanthomas (in Achilles tendon) - Heterozygotes = 300 mg/dL - Homozygotes= +700 mg/dL |
-familial hypercholesterolemia (hyperlipidemia type IIA)
|
|
Autosomal-dominant disease
- telangiectasia - recurrent epistaxis - skin discolorations - arteriovenous malformations |
- Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
|
|
Autosomal-dominant disease
- defect w/spectrin or ankyrin - hemolytic anemia - increased MCHC |
- Hereditary spherocytosis
|
|
Autosomal-dominant disease
- depression, progressive dementia, choreiform movements - decrease levels of GABA and ACh in brain - located on chromosome 4 |
- Hunting disease
|
|
Autosomal-dominant disease
- aortic incompetence/ aortic dissection - floppy mitral valve - fibrillin gene mutation |
- Marfan syndrome
|
|
Autosomal-dominant disease
- associated w/ ret gene - familial tumors of endocrine glands - pancreas, parathyroid, pituitary, thyroid, and adrenal medulla |
- Multiple endocrine neoplasia (MEN 1,2A,2B)
|
|
Autosomal-dominant disease
- cafe-au-lait spots - Lisch nodules (pigmented iris hamartomas) - skeletal disorders - optic pathway gliomas - long long arm of chromosome 17 |
- Neurofibromatosis type 1 (von Recklinghausen's)
|
|
Autosomal-dominant disease
- bilateral acoustic schwannomas - juvenile cataracts - on chromosome 22 |
- Neurofibromatosis type 2
|
|
Autosomal-dominant disease
- facial lesions (adenoma sebaceum) - hypopigmented "ash leaf spots" - cortical and retinal hamartomas - seizures and retardation - renal cyst and angiomyolipomas - rhabdomyomas |
- Tuberous sclerosis
|
|
Autosomal-dominant disease
- hemangioblastomas of retina - bilateral renal cell carcinomas - associated w/ deletion of VHL gene on chromo. 3 - constitutive expression of HIF |
- von Hippel-Lindau disease
|
|
Autosomal-recessive diseases
|
- Albinism
- ARPKD - cystic fibrosis - glycogen storage diseases - hemochromatosis - mucopolysaccharidoses (except Hunter's) - phenylketonuria "PKU" - sickle cell anemias - sphingolipidoses (except Fabry's) - thalassemias |
|
- Autosomal-recessive defect in CFTR on chromo. 7
- deletion of Phe 508 - mutation causes abnormal protein folding resulting in degradation of channel - defective Cl- channel "thick mucus in lungs, pancreas, and liver" - recurrent pulmonary infections - meconium ileus in newborns |
Cystic Fibrosis
|
|
Diagnostic test for Cystic Fibrosis
|
sweat test (increased concentration of Cl- ions)
|
|
Treatment for Cystic Fibrosis
|
N-acetylcysteine
|
|
X-linked recessive disorders
(Be Wise, Fool's GOLD Heeds Silly Hope) |
- Bruton's agammaglobulinemia
- Wiskott-Aldrich syndrome - Fabry's disease - G6PD deficiency - Ocular albinism - Lesch-Nyhan syndrome - Duchenne's (Becker's) muscular dystrophy - Hunter's Syndrome - Hemophilia A and B |
|
- deletion of dystrophin gene
- x-lined frame shift mutation (deletion) - accelerated muscle breakdown - pseudohypertrophy of calf muscles due to fibrofatty - uses Gower's maneuver (hands aid in getting up) - onset before 5 years of age |
Duchenne's muscular dystrophy
|
|
- X-linked mutated dystrophin gene
- less severe muscle breakdown - in frameshift (no deletion) |
Becker's muscular dystrophy
|
|
Diagnoses of muscular dystrophies
|
increased CPK and muscle biopsy
|
|
- Findings: macro-orchidism, long face with a large jaw, large everted ears autism, and mitral valve prolapse
- 2nd most common cause of genetic retardation - X-linked defect in the methylation and expression of the FMR1 gene (associated w/chromosomal breakage) "CGG" |
Fragile X syndrome
|
|
Trinucleotide repeat expansion diseases
|
- Huntington's disease
- myotonic dystrophy - Friedreich ataxia - fragile X syndrome |
|
Trinucleotide repeat expansion disease
- Huntington's disease: repeat |
(CAG)
|
|
Trinucleotide repeat expansion disease
- myotonic dystrophy |
(CTG)
|
|
Trinucleotide repeat expansion disease
- Friedreich ataxia |
(GAA)
|
|
Trinucleotide repeat expansion disease
- fragile X syndrome |
(CGG)
|
|
Autosomal trisomies
- Findings: retardation, flat facies, epicanthal fold, simian crease, duodenal atresia - ASD, ALL, Alzheimer's disease - due to meiotic nondisjunction (advance maternal age) |
Down syndrome (t21)
|
|
Autosomal trisomies
- Findings: retardation, rockers bottom feet, micrognathia (small jaw), clenched hands - death within 1 year of birth |
Edward's syndrome (t18)
|
|
Autosomal trisomies
- Findings: cleft lip/palate, holoprosencephaly, polydactyly - death within 1 year of birth |
Patau's syndrome (t13)
|
|
Most common trisomy resulting in abortion (not viable for life)
|
t16
|
|
- congenital microdeletion of short arm of chromosome 5
- Finding: high-pitched crying/mewing; VSD |
Cri-du-chat syndrome
|
|
Down syndrome screening test
|
1- decreased alpha-fetoprotein
- decreased estriol - increased beta-hCG - increased inhibind 2- ultrasounds shows increase nuchal translucency |
|
- congenital microdeletion of long arm of chromosome 7 (region includes elastin gene)
- "elfin" facies - hypercalcemia (sensitive to vit-D) - well-developed verbal skills - extremely frendingly with strangers |
Williams syndrome
|
|
due to aberrant development of 3rd/4th bronchial pouches
|
DiGeorge syndrome (22q11)
|
|
Fat soluble vitamins
|
A,D,E,K
|
|
Water soluble vitamins
|
B1-6; B12; C; Biotin, and Folate
|
|
Water soluble vitamins store in the liver
|
B12 and folate
|
|
result of B-complex vits deficiencies
|
dermatitis, glossitis, and diarrhea
|
|
Retinol
|
Vitamin A
|
|
Thiamine
|
Vitamin B1
|
|
Rivoflavin
|
Vitamin B2
|
|
Niacin
|
Vitamin B3
|
|
Pantothenate
|
Vitamin B5
|
|
Pyridoxine
|
Vitamin B6
|
|
Cobalamin
|
Vitamin B12
|
|
Ascorbic acid
|
Vitamin C
|
|
Vitamin A: Function
|
- Antioxidant
- visual pigments - epithelial cells into specialized pancreatic cells - used to treat measles |
|
Vitamin A: Deficiency
|
- night blindness
- dry skin |
|
Vitamin A: Excess
|
- alopecia
- Teratogenic: (cleft palate, cardiac abnormalities) - pregnancy test before isotRETINOin is prescribed |
|
Vitamin B1: Function
|
cofactor for
- Pyruvate dehydrogenase - alpha-ketoglutarate dehydrogenase - Transketolase - Branched-chain AA dehydrogenase |
|
Vitamin B1: Deficiency
|
- impaired glucose breakdown -> ATP depleted
- Wernicke-Korsakoff syndrome - Beriberi (Dry/Wet) |
|
- confusion
- ophthalmoplegia - ataxia + confabulation - personality changes - memory loss (permanent) |
Wernicke-Korsakoff
|
|
Damaged in Wernicke-Korsakoff
|
Medial dorsal nucleus of thalamus, mamillary bodies
|
|
Thiamine deficiency: polyneuritis, symmetrical muscle wasting
|
Dry Beriberi
|
|
Thiamine deficiency: high-output cardiac failure (dilated cardiomypathy), edema
|
Wet Beriberi
|
|
Vitamin B2: Function
|
Cofactor in oxidation and reduction (FADH2)
|
|
Vitamin B2: Deficiency
|
The 2 C's
- Cheilosis (lip inflammation, fissure a mouth corner) - Corneal vascularization |
|
Vitamin B3: Function
|
- Constituent of NAD+ and NADP+
- derived from tryptophan - synthesis requires B6 |
|
Vitamin B3: Deficiency
|
The 3 D's
- Diarrhea (carcinoid syndrome) - Dermatitis (pellagra caused by Hartnup disease) - Dementia (glossitis) |
|
Vitamin B3: Excess
|
Facial flushing
(due to pharmacologic doses for treatment of hyperlipidemia) |
|
Vitamin B5: Function
|
Essential component of CoA (cofactor for acyl transfers) and fatty acid synthase
|
|
Vitamin B6: Function
|
- cofactor used in transamination (ALT, AST) & heme synthesis
- required for the synthesis of niacin from trytophan |
|
Vitamin B6: Deficiency
|
- convulsions
- sideroblastic anemia - inducible by INH and oral contraceptives |
|
Vitamin B12: Function
|
Cofactor for homocysteine methyltransferase & methylmalonyl-CoA mutase
(very large reserve pool in liver "several years") |
|
Vitamin B12: Deficiency
|
- Macrocytic, megaloblastic anemia
- hypersegmented PMNS - neurologic symptoms - prolong -> irreversible nerve damage |
|
Vitamin B12 deficiency cause
|
- Diphyllobothrium latum
- lack of intrinsic factor (pernicious anemia; gastric surgery) - Crohn's disease (absent terminal ileum) |
|
Test used to detect the etiology of vitamin B12 deficiency
|
Schilling test
|
|
Folic acid: Function
|
- important for the synthesis of nitrogenous bases in DNA and RNA
- converted to tetrahydrofolate (THF), a coenzyme for 1-carbon transfer/methylation reactions |
|
Folic acid: Deficiency
|
- Macrocytic, megaloblastic anemia
- Most common vit deficiency - seen in alcoholism and pregnancy - *no neurologic symptoms* |
|
Drugs that can cause folic acid deficiency
|
- Phenytoin
- sulfonamides - MTX |
|
S-adenosyl-methionine (SAM): Function
|
- methyl donor
- dependent on vit B12 and folate - required for conversion of NE to epinephrine |
|
Biotin cofactor for...
|
- Pyruvate carboxylase (gluconeogenesis)
- Acetyl-CoA carboxylase (fatty acid synthesis) - Propionyl-CoA carboxylase (Beta Oxidation) |
|
Biotin: Deficiency
|
- dermatitis, alopecia, enteritis
- caused by antibiotic or raw eggs - relatively rare |
|
Vitamin C: Function
|
- Antioxidant
- iron reabsorption by keeping iron in Fe2+ state (ferrus) - needed for hydroxylation of proline and lysine in collagen synthesis - Dopamine-beta-hydroxylase (convert dopamine to NE) |
|
Vitamin C: Deficiency
|
Scurvy
- swollen gums - bruising - poor wound healing Weakened immune response |
|
Vitamin D ingested from plants
|
D2- ergocalciferol
|
|
Vitamin D consumed in milk, formed in sun-exposed skin
|
D3- cholecalciferol
|
|
Vitamin D storage form
|
25-OH D3
|
|
Vitamin D active form
|
1,25-(OH)2 D3
|
|
Vitamin D: Function
|
- increase intestinal absorption of calcium and phosphate
- increase bone resorption |
|
Vitamin D: Deficincey
|
- Rickets- kids
- Osteomalacia- adults - tetany |
|
Vitamin E: Function
|
Antioxidant for erythrocytes and membranes
|
|
Vitamin E: Deficiency
|
- Fragile erythrocytes (hemolytic anemia)
- posterior column and spinocerebellar tract demyelination |
|
Vitamin K: Function
|
- Catalyzes gamma-carboxylation of glutamic acid (blood clotting)
- Synthesized by intestinal flora |
|
Vitamin K: Deficiency
|
- Neonatal hemorrhage w/ increased PT/aPTT, but normal bleed time (give at birth)
- can occur after prolong use of broad-spectrum antibiotics |
|
Zinc: Function
|
- Essential for the activity of 100+ enzymes
- formation (transcription factor motif) |
|
Zinc: Deficiency
|
- delayed wound healing
- hypogonadism - decreased adult hair (face, axilla, pubic) - anosmia - predisposed to alcohol cirrhosis |
|
- Antidote for methanol or ethylene glycol poisoning
- inhibits alcohol dehydrogenase |
Fomepizole
|
|
Protein malnutrition resulting in:
- skin lesions - edema - liver malfunction (fatty) child w/swollen belly |
Kwashiorkor
|
|
Energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat, and variable edema.
|
Marasmus
|
|
Metabolism sites:
- in the Mitochondria |
- fatty acid (beta) oxidation
- acetyl-CoA production - TCA cycle - oxidative phosphorylation |
|
Metabolism sites:
- in the Cytoplasm |
- Glycolysis
- fatty acid synthesis - HMP shunt - protein synthesis (RER) - steroid synthesis (SER) |
|
Metabolism sites:
- in the Cytoplasm & Mitochondria |
- Heme synthesis
- Urea cycle - Gluconeogenesis |
|
Enzyme terminology
- uses ATP to ADD high-energy phosphate group onto substrate "to make" |
Kinase
|
|
Enzyme terminology
- oxidizes substrate (creates extra NADPH2 & FADH2) |
Dehydrogenase
|
|
Enzyme terminology
- adds 1 carbon w/the help of biotin |
Carboxylase
|
|
Rate-determining (limiting) enzyme
- Glycolysis |
Phosphofructokinase-1 (PFK-1)
|
|
Rate-determining (limiting) enzyme
- Gluconeogenesis |
Fructose-1,6-bisphosphatase
|
|
Rate-determining (limiting) enzyme
- TCA cycle |
Isocitrate dehydrogenase
|
|
Rate-determining (limiting) enzyme
- Glycogen synthesis |
Glycogen synthase
|
|
Rate-determining (limiting) enzyme
- Glycogenolysis |
Glycogen phosphorylase
|
|
Rate-determining (limiting) enzyme
- HMP shunt |
G6PD (glucose-6-phosphate dehydrogenase)
|
|
Rate-determining (limiting) enzyme
- De novo pyrimidine synthesis |
carbamoyl phosphate synthetase II
|
|
Rate-determining (limiting) enzyme
- De novo purine synthesis |
Glutamine-PRPP amidotransferase
|
|
Rate-determining (limiting) enzyme
- Urea cycle |
Carbamoyl phosphate synthetase I
|
|
Rate-determining (limiting) enzyme
- Fatty acid sythesis |
Acetyl-CoA carboxylase
|
|
Rate-determining (limiting) enzyme
- Fatty acid (beta) oxidation |
Carnitine acyltransferase I
|
|
Rate-determining (limiting) enzyme
- Ketogenesis |
HMG-CoA synthase
|
|
Rate-determining (limiting) enzyme
- Cholesterol synthesis |
HMG-CoA reductase
|
|
First step in glycolysis and glycogen synthesis in the liver
|
Hexokinase/glucokinase
|
|
Feedback inhibition for hexokinase
|
glucose-6-phosphate
|
|
Inhibits lipoic acid
Findings: vomiting, rice water stools, garlic breath |
Arsenic posioning
|
|
Electron transport chain
- site of NADH+ -> NAD+ |
Complex I
|
|
Electron transport chain
- site of FADH2+ -> FAD+ |
Complex II
|
|
Electron transport chain
- site of 1/2 O2 ->H2O |
Complex IV
|
|
Electron transport chain
- site of ADP -> ATP |
Complex V
|
|
Oxidative phosphorylation poison
- Directly inhibit electron transport, causing a decrease proton gradient and block ATP synthesis |
Electron transport inhibitors
- Rotenone - cyanide (CN) - antimycin A - carbon monoxide |
|
Oxidative phosphorylation poison
- Directly inhibit mitochondrial ATPase, causing an increase proton gradient. No ATP is produced because electron transport stops |
ATPase inhibitor
- Oligomycin |
|
Oxidative phosphorylation poison
- increase permeability of membrane, causing a decrease proton gradient. ATP synthesis stops, but electron transport continues. Produces heat. |
Uncoupling agents
- 2,4-DNP - aspirin - thermogenin in brown fat |
|
Cannot participate in gluconeogenesis because it lacks G-6-P (glucose-6-phosphatase)
|
Muscle
|
|
Essential fructosuria
- Signs/symptoms |
Fructose appears in blood and urine
|
|
Essential fructosuria
- Defect |
Fructokinase
|
|
Fructose intolerance
- Signs/symptoms |
- hypoglycemia
- jaundice - cirrhosis - vomiting |
|
Fructose intolerance
- Defect |
Aldolase B
|
|
Treatment for fructose intolerance
|
decrease both fructose and sucrose
|
|
Galactokinase deficiency
- Sign/symptoms |
- galactose in blood and urine
- infantile cataracts - failure to track objects - failure to develop a social smile |
|
Classic galactosemia
- Defect |
absence of galactose-1-phosphate uridyltransferase (UT)
|
|
Classic galactosemia
- Sign/symptoms |
- jaundice
- hepatomegaly - infantile cataracts - mental retardation - failure to thrive |
|
Treatment for Classic galactosemia
|
excluded galactose and lactose from diet
|
|
Essential Amino acids
|
- phenylalanine
- valine - threonine - tryptophan - methionine - leucine - isoleucine - lysine - histidine - arginine |
|
Acidic amino acids
|
- Aspartic acid
- Glutamine |
|
Basic amino acids
|
- Arginine
- Lysine - Histidine |
|
The most basic amino acid
|
Arginine
|
|
Amino acid w/no charge at body pH
|
Histidine
|
|
Amino acids required during period of growth (childhood)
|
Arginine and Histidine
|
|
Sign/symptom: tremor, slurring speech, somnolence, vomiting, cerebral edema, blurred vision
Labs: excess NH+4; depletes alpha-ketoglutarate; inhibition of TCA cycle |
Hyperammonemia
|
|
Treatment for Hyperammonemia
|
- limit protein in diet
- Benzoate or phenylbutyrate (lower ammonia levels) |
|
Excess of this in (OTC) ornithine transcarbamylase deficiency
|
carbamoyl phosphate -> orotic acid
|
|
(OTC) ornithine transcarbamylase deficiency
- Findings |
- orotic acid in blood and urine
- decrease BUN - hyperammonemia |
|
(OTC) ornithine transcarbamylase deficiency vs Orotic aciduria
|
OTC has decrease BUN and hyperammonemia
|
|
Amino acid derivative
- tyrosine -> Thyroxine (T3,T4) - Dopa -> melanin - Dopamine - NE - Epinephrine |
Phenylalanine
|
|
Amino acid derivative
- Niacin -> NAD+/NADP+ - Serotonin -> Melatonin |
Tryptophan
|
|
Amino acid derivative
- Histamine |
Histidine
|
|
Amino acid derivative
- Porphyrin -> Heme |
Glycine
|
|
Amino acid derivative
- Creatine - Urea - NO (nitric oxide) |
Arginine
|
|
Amino acid derivative
- GABA - Glutathione |
Glutamate
|
|
Phenylketonuria
- Defect |
- decreased phenylalanine hydroxylase
- decreased tetrahydrobiopterin cofactor - Tyrosine become essential |
|
Phenylketonuria
- Presentation |
- Mental retardation
- growth retardation - musty body odor - fair skin, eczema |
|
Alkaptonuria (ochronosis)
- Defect |
- deficiency of homogentisic acid oxidase
- no tyrosine to fumarate |
|
Alkaptonuria (ochronosis)
- Presentation |
- dark connective tissue
- brown pigmented sclera - urine turns black on standing - may have debilitating arthralgias |
|
Homocystinuria
- Defect |
- cystathionine synthase deficiency
- decreased affinity of cystathionine synthase - homocysteine methyltransferase deficiency |
|
Homocystinuria
- Presentation |
- increased homocysteine in urine
- mental retardation - osteoporosis - tall stature - atherosclerosis (stroke/MI) - kyphosis, lens subluxation |
|
Treatment for cystathionine synthase deficiency
|
- Met, Cys, B12, and folate
|
|
Albinism
- Defect |
- Tyrosinase
- defective tyrosine transporters |
|
Cystinuria
- Defect |
Hereditary defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in the PCT of kidney
|
|
Cystinuria
- Presentation |
- excess cystine in urine -> cystine stones (staghorn)
|
|
Bond between two cystine
|
Disulfide
|
|
Maple syrup urine disease
- Defect |
- decreased alpha-ketoacid dehydrogenase
blocked degradation of branched amino acids - Isoleucine - Leucine - Valine |
|
Maple syrup urine disease
- Presentation |
- increased alpha-ketoacids in urine
- CNS defects (mental retardation) - death |
|
Hartnup
- Defect |
Defective neutral acid transporter on renal and intestinal epithelial
|
|
Hartnup
- Presentation |
- Tryptophan excretion in urine
- decreased tryptophan absorption in gut - PELLAGRA |
|
Glycogen storage disease
Findings: - severe fasting hypoglycemia - increased glycogen in liver - increased blood lactate - hepatomegaly Deficient enzyme: ? |
Glucose-6-phosphatase
|
|
Glycogen storage disease
Findings: - cardiomegaly and systemic findings - leading to early death (2 yrs of age) Deficient enzyme: ? |
Lysosomal alpha-1,4 glucosidase
(acid maltase) |
|
Glycogen storage disease
Findings: - milder hypoglycemia - w/normal blood lactate levels - gluconeogenesis is intact Deficient enzyme: ? |
alpha-1,6-glucosidase
(Debranching enzyme) |
|
Glycogen storage disease
Findings: - increased glycogen in muscle - leading to muscle cramps - myoglobinuria w/strenuous exercise (lactate) Deficient enzyme: ? |
Glycogen phosphorylase
|
|
Lysosomal storage disease
Fabry's disease - Findings: ? |
- peripheral neuropathy of hands/feet
- angiokeratomas - cardio/renal disease |
|
Lysosomal storage disease
Gaucher's disease - Findings: ? |
- Hepatosplenomegaly
- aseptic necrosis of the head of the femur - Gaucher's cells (macrophages look like crumpled tissue paper) |
|
Lysosomal storage disease
Niemann-Pick disease - Findings: ? |
- progressive neurodegeneration
- hepatosplenomegaly - cherry-red macula - foam cells |
|
Lysosomal storage disease
Tay-Sachs disease - Findings: ? |
- progressive neurodegeneration
- cherry-red macula - lysosomes w/onion skin |
|
Lysosomal storage disease
Metachromatic leukodystrophy (MML) - Findings: ? |
- Central and peripheral demyelination w/ataxia
- dementia |
|
Lysosomal storage disease
Hurler's syndrome - Findings: ? |
- Gargoylism
- corneal clouding - airway obstruction (vs. I cell) |
|
Lysosomal storage disease
Hunter's syndrome - Findings: ? |
- personality changes + aggressive behavior
- no corneal clouding |
|
Lysosomal storage disease
Findings: - peripheral neuropathy of hands/feet - angiokeratomas - cardio/renal disease Deficient enzyme: ? |
alpha-galactosidase A
|
|
Lysosomal storage disease
Findings: - Hepatosplenomegaly - aseptic necrosis of the head of the femur - Gaucher's cells (macrophages look like crumpled tissue paper) Deficient enzyme: ? |
beta-glucocerebrosidase
|
|
Lysosomal storage disease
Findings: - progressive neurodegeneration - hepatosplenomegaly - cherry-red macula Deficient enzyme: ? |
Sphingomyelinase
|
|
Lysosomal storage disease
Findings: - progressive neurodegeneration - cherry-red macula - lysosomes w/onion skin Deficient enzyme: ? |
Hexosaminidase A
|
|
Lysosomal storage disease
Findings: - Central and peripheral demyelination w/ataxia - dementia Deficient enzyme: ? |
Arylsulfatase A
|
|
Lysosomal storage disease
Findings: - Gargoylism - corneal clouding - airway obstruction (vs. I cell) Deficient enzyme: ? |
alpha-L-inuronidase
|
|
Lysosomal storage disease
Findings: - personality changes + aggressive behavior - no corneal clouding Deficient enzyme: ? |
Iduronate sulfatase
|