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90 Cards in this Set
- Front
- Back
Leukocyte Adhesion Deficiency Type I
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Defect in biosynthesis of B2 integrins
B-2 integrins bind to ICAM -1 causes firm adhesion deficiency results in impaired leukocyte activation and recurrent bacterial infections Diagnosed by flow cytometry |
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Leukocyte Adhesion Deficiency Type 2
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absence of sialyated oligosacch. receptor for endothelial cell selectins
causes a deficiency in rolling results in impaired leukocyte activation and recurrent bacterial infections diagnosed by flow cytometry |
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Exogenous Chemoattractants
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soluble bacterial products
N-formly methionine terminal amino acids |
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Endogenous chemoattractants
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Complement metabolites (c5a)
AA metabolites (leukotriene B4) Cytokines (Il-8) |
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Chronic Granulomatous Disease
X-Linked |
defect in membrane NADPH oxidase
CGD results in recurrent bacterial infections, especially catalase positive bacteria Diagnosis: Nitroblue tetrazolium (NBT) test -testing capacity of neutrophils to reduce NBT to formazan yielding a blue pigment -In CGD, no blue pigment is identified |
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Chronic Granulomatous Disease
Autosomal recessive |
defect in cytoplasmic NADPH oxidase
AC= air conditioner Diagnosis: Nitroblue tetrazolium (NBT) test -testing capacity of neutrophils to reduce NBT to formazan yielding a blue pigment -In CGD, no blue pigment is identified |
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Myeloperoxidase Deficiency
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Absent H2O2-MPO system
most common neutrophil defect Recurrent bacterial infections |
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Chediak-Higashi Syndrome
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1. Autosomal recessive
2. Lysosomes cannot fuse phagosome , thus they become giant-sized 3. Results in neutropenia, recurrent infections, defective degranulation, problems with migration and chemotaxis 4. Some clinical features include albinism, nerve defects, bleeding, immunodeficiency due to defects in organelle membrane fusion |
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Cellulitis
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spreading of inflammation in a solid tissue
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Ulcer
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localized defect in the surface of an organ or tissue due to sloughing of inflammatory necrotic debris
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Paroxysmal nocturnal hemoglobinuria (PNH)
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Deficiency of DAF → Intravascular hemolysis/anemia
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Hereditary angioneurotic edema (HAE)
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Deficiency of C1 inhibitor
1. Swelling of skin, larynx, intestines 2. Stress, trauma |
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Epidermal Derived growth factor (EGF)
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mitogenic (stimulates mitosis) for a variety of epithelial cells and fibroblasts
causes hepatic cell division in vivo TGF alpha binds to the same receptors and produces the same effects |
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Platelet Derived growth factor
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stored in alpha granules of platelet cells
causes migration and proliferation of 1. fibroblasts 2. smooth muscle 3. monocytes produced by: 1. activated macrophages 2. endothelial cells 3. smooth muscle cells 4. many tumor cells |
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Fibroblast growth factor
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causes angiogenesis
development hematopoisesis |
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Vascular endothelial growth factor
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vascular permeability factor
vasculogenesis angiogenesis |
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Migration and proliferation of fibroblasts
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TGF-beta
PDGF EGF FGF IL-1 TNF - alpha |
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Deposition of ECM
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VEGF
FGF |
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Collagen synthesis
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PDGF
FGF TGF-B IL-1 and IL-4 |
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Benzanthracine
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skin cancer
sarcomas |
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Benzopyrene in tobacco smoke
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lung cancer
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beta-napthalamine
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bladder cancer
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nitrosamine
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gastric cancer
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nitroso compounds in tobacco smoke
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lung cancer
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asbestos
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lung cancer
mesothelioma - malignant tumor of the pleura |
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Vinyl Chloride
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hemangiosarcoma of the liver
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arsenic
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skin cancer
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chromium, nickel, or other heavy metals
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lung cancer
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aflatoxin
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liver cancer
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Hepatitis B and C
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hepatocellular carcinoma
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epstein-barr virus
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burkitt's lymphoma
nasopharyngeal carcinoma |
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Herpes Virus type II
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warts
cervical cancer |
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HPV
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warts
cervical cancer |
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HTLV-1
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adult T-cell Leukemia/lymphoma
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HIV -1
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Kaposi's Sarcoma
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UV rays
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squamous cell carcinoma
basal cell carcinoma malignant melanoma |
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X-Rays
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skin cancer
bone cancer |
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miners of radioactive elements
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lung cancer
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atom bomb radiation
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leukemia
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theraputic radiation to the head and neck
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thyroid cancer
former treatment for acute tonsillitis |
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thorium
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liver cancer
formerly used as a contrast medium |
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Li-Fraumeni syndrome
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inherited mutant p53
predisposes to a wide range of tumors |
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Chronic myelgenous leukemia (CML)
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translocation 9:22
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Burkitt's lymphoma
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translocation 8:14
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Retinoblastoma
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deletion 13
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Wilm's tumor
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deletion 11
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neuroblastoma
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N-myc gene amplification
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Carcinoembryonic Ag (CEA)
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colorectal, pancreatic, liver, gastic cancers
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Alpha-fetoprotein (AFP)
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liver cancer, germ line tumors of testis
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Prostatic Specific Ag (PSA)
Prostatic Acid Phosphatase (PAP) |
prostate cancer
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Human Chorionic Gonadotropin (HCG)
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trophoblastic tumors, germ cell tumors
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Carcinoma of the Lung
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1. Local Growth & Extension: encircle bronchus, extend to esophagus, parietal pleura, brachial plexus, mediastinum
2. Implantation: pleura seeding and effusion 3. Metastasis: a. Lymphatic: tracheobronchial, mediastinal, scalene nodes b. Hematogenous: adrenal/bone (common); liver, kidney, brain |
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Carcinoma of Colon & Rectum
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1. Local Growth & Extension: fungating, ulcerative or stenotic; extend to serosa and nearby organs
a. Right-sided: usually large fungating masses b. Left-sided: usually stenotic (apple-core lesions) c. Common Presentation: alternating diarrhea and constipation 2. Implantation: peritoneal seeding after extension through serosa 3. Metastasis: a. Lymphatic: mesenteric nodes b. Hematogenous: liver via portal system; can then affect lung |
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Carcinoma of the Breast
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1. Local Growth & Extension: hard scirrhous or bulky soft medullary mass; may have intra-epidermal extension; nipple inversion, peau d’orange (due to blocked lymphatics)
a. Hard Scirrhous: desmoplastic adenocarcinomas b. Bulky Soft: medullary carcinomas 2. Metastasis: a. Lymphatic: axillary, internal mammary, supraclavicular nodes; opposite breast b. Hematogenous: lung, liver, bone, adrenal, ovary, brain |
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Carcinoma of the Prostate
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1. Local Growth & Extension: stony hard mass on posterior lobe; extend to: seminal vesicles, bladder base, rectum, urethra
2. Metastasis: a. Lymphatic: pelvic, periaortic nodes b. Hematogenous: bone- osteoblastic (*unusual- most lesions are osteolytic*); lung, testis, adrenal |
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Carcinoma of the Cervix
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1. Local Growth & Extension: vaginal wall, ureters, urinary bladder
a. Can lead to: urethral obstruction, pyelonephritis, uremia (renal failure is common cause of death) 2. Metastasis: a. Lymphatic: regional lymph nodes |
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Epithelial
(tumor Marker in tissue) |
keratin
epithelial membrane Ag (EMA) Carcinoembryonic Ag (CEA) |
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Mesenchymal
(tumor Marker in tissue) |
vimentin
desmin |
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Nerve, Neuroendocrine
(tumor Marker in tissue) |
Neuron specific enolase (NSE)
chromogranins |
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Prostate
(tumor Marker in tissue) |
Prostate specific Ag (PSA)
Prostatic Acid phosphatase (PAP) |
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Lymphomas
(tumor Marker in tissue) |
Leukocyte common Ag (LCA
T and B cell markers |
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Endocrine
(tumor Marker in tissue) |
hormones
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Carcinoembryonic Ag (CEA)
(tumor Marker in blood) |
Colorectal
pancreatic liver gastric cancers |
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Alpha fetoprotein (AFP)
(tumor Marker in blood) |
liver cancer
germlkine tumors of testis |
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PSA
PAP (tumor Marker in blood) |
prostate cancer
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HCG
(tumor Marker in blood) |
trophoblastic tumors
germ cell tumors |
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Marfan Syndrome
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A connective tissue disorder
Autosomal Dominant Features 1. very tall thin patient 2. Disproportionate tall stature 3. Arachnodactyly 4. Pectus excavatum - dent in chest 5. myopia (near sightedness) 6. upward lens dislocation 7. Mitral valve prolapse 8. thoracic aortic root dilates and dissects Genetics 1. 30% new mutations 2. Fibrillin gene defect 3. incidence 1/5000 pectus excavatum |
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Neurofibromatosis Type 1 (NF1)
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Autosomal dominant
Features 1. Skin: Café au laits (more than 6), axillary freckling (most people shouldn’t have these), neurofibromas (benign tumors) 2. Eyes: Lisch nodules (benign tumors), optic glioma (benign tumors on the optic nerve) 3. Neurological: may have Complex Learning disability (usually a visual-spatial disability… they are not mentally retarded) 4. Rare: a. one of the benign tumors can transform into cancer, so follow the patient overtime b. pheochromocytoma C. Genetics: 1. incidence: 1/3000 2. Neurofibromin gene on chromosome 17; a tumor suppressor gene NT note: the tumor suppressor gene is defective, therefore it is not “applying the brakes” to cellular proliferation, and multiple tumors are able to form, as in NF1. 3. 50% are new mutations |
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Ehlers-Danlos Syndromes
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a group of connective tissue disorders
Autosomal Dominant Types I through IV Features: 1. Skin: hyperextensible, keloids (abnormal scar formation) 2. Joints: hypermobile 3. Artery and viscera rupture (Type IV) can be an immediate cause of death. 4. Retinal detachment (Type VI) 5. Diaphragmatic hernia (Type I) 1. Genetic heterogeneity: mutations at several loci (genes) produce same trait. In other words, several different gene mutations cause similar disorders |
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Familial Hypercholesterolemia
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Autosomal Dominant
C. Features 1. These individuals have cholesterol levels 3 to 6 times the normal level. 2. Xanthomas, premature atherosclerosis 3. These individuals may have a myocardial infarct (MI) as early as 20 years of age. Genetics 1. Most common Mendelian disorder 2. 3-6% of the survivors of myocardial infarctions have familial hypercholesterolemia. 3. Incidence: 1/500 4. LDL receptor gene on chromosome 19 is defective however there are over 900 different mutations including deletions and point mutations. Therefore, it is very difficult to diagnosis at the molecular level because you must know the specific mutation that you are looking for. |
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Autosomal Dominant Polycystic Kidney Disease
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Autosomal Dominant
Features: 1. Large kidneys with multiple, bilateral cysts 2. Individuals end up in renal failure by the age of about 50. 3. 40% of the time the individuals have cyst in other organs or berry aneurysms. The classic example is hepatic cysts. (Common USMLE question). 4. Berry aneurysms are dilations in the anterior half of the Circle of Willis (right hand lower picture) These aneurysms cause 10% of adult polycystic kidney disease deaths. 5. 25% of the time there are heart defects; most commonly mitral valve prolapse. 6. Even though the name of the disorder “says” it’s a kidney disease, it’s a systemic disorder. Genetics: 1. Incidence: 1/600; very common and you will definitely see it on the wards. 2. 5-10% of the individuals with chronic renal failure will have this disease 3. Genetic heterogeneity: The PKD1 gene on chromosome 16 is the mutation that causes the disease 85% of the time and the PKD2 gene chromosome 4 is the culprit 15% of the time. Remember, different mutations, same disorder. |
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Tuberous Sclerosis
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Autosomal Dominant
B. Features 1. ‘Tubers’ (tumors) = fibromas in the brain, kidney, eye, heart & fingernails (seen in the top photo). These tumors can be passed off as warts and the diagnosis can be missed. 2. Skin: hypopigmented patches (seen in the bottom photo), “sort of the opposite of the café-au-lait” 3. CNS: a. mental deficiency. Associated much more with mental retardation. Remember in NF1 the patients are not mentally retarded. b. Classically presents with seizures. C. Genetics 1. Genetic heterogeneity: Tuberin gene on chromosome 16 & Hamartin gene on chromosome 9. 2. Has variable expressivity = autosomal dominant trait is expressed differently in affected individuals |
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Achondroplasia
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causes dwarfism
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B.Huntington’s disease
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Autosomal dominant
have choreiform movements, adult onset |
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C.Osteogenesis Imperfecta
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broken bones all over the body
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D.Apert Syndrome
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Craniosynostosis (fused sutures in the head), hand & feet anomalies
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XVIII. Tyrosinase-Negative Albinism
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Autosomal Recessive
1. Little pigmentation in skin, hair and eyes 2. Nystagmus: rapid involuntary rhythmic eye movement 3. strabismus: “cross-eyed” (eyes do not point in the same direction) C. Genetics: Tyrosinase gene mutation on chromosome 11 that results in decreased melanin |
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Phenylketonuria
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Autosomal recessive
A. Features: 1. Fair pigmented 2. “Mousy” “attic-like” odor at birth 3. Overly attractive children, “cute cute cute cute kids” according to Dr. McGoey’s experience. 4. If left untreated, the child will develop mental retardation, seizures & paraplegia. 5. If treated the children are relatively normal. a. Nationwide screenings for PKU are done (mandatory) for newborns a couple weeks after birth to avoid the severe neurological damage. B. Treatment: a severe dietary restriction of phenylalanine C. Genetics: 1. Incidence: 1/10,000 whites 2. Defect in the Phenylalanine hydroxylase gene on chromosme 12 |
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XX. Sickle Cell Anemia
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Autosomal Dominant
B. Clinical: 1. Anemia 2. Pain crises 3. Priapism – a sustained very painful erection can occur in a child. 3. Autosplenectomy and infections – spleen becomes infarcted due to vasoclussive crisis, therefore there is an increase likelihood of infections. Therefore vaccines are given to these individuals. C. Morphologic Features: Howell Jolly bodies (purple things inside RBCs) & Sickled RBCs (drepanocytes) D. Genetics: b globin gene mutation on chromosome 11; Missense mutation: glutamate to valine |
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XXI. Cystic Fibrosis
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Autosomal recessive
failure to thrive, microcephaly, nasty sputum production & constantly on antibiotics due to recurring infections. B. Features: Recurrent infections, cirrhosis, diabetes, pancreatic insufficiency, bronchiectasis (dilated bronchi seen in the top picture often filled with pus, infection, & mucus), death in 20s C. Genetics: 1. Most common lethal genetic disease of Caucasians 2. Incidence: 1/3200 in Caucasians, 1/22 Caucasians are carriers a. There is a movement to offer CF testing to all Caucasians thinking of becoming pregnant. D. Chloride channel (CFTR) gene mutation on chromosome 7 |
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XXII. Lysosomal Storage Diseases (LSDs)
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Autosomal recessive
A. Involves the lysosomal enzymes that are responsible for the breakdown of complex molecules. C. Lysosomes store things that they shouldn’t be storing. D. Disease is classified according to the nature of the accumulated metabolite 1. Glycogenoses: Disease = Pompe (won’t discuss at present) 2. Sphingolipidoses: Disease = Tay Sachs, Gaucher, Neimann-Pick 3. Mucopolysaccharidoses Diseases: Hurler (type I) & Hunter (type II) |
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E. Sphingolipodosis LSD: Tay Sachs
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Tay Sachs Disease
Features 1. progressive blindness 2. cherry red retinal spot seen via fundoscopic exam), --> not specifice but associated with it 3. decline in developmental milestones, 4. seizures, 5. mental retardation; 6. Death at 2-3 years Genetics: Hexosaminidase A gene on chromosome |
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F. Sphingolipidosis LSD: Gaucher Disease
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1. Clinical:
a. Type I (99%): adults, splenomegaly, bone pain and fractures b. Type II: infants, hepatosplenomegaly, seizures, mental retardation and early death c. Type III: juvenile form, intermediate prognosis NT note: Just know that there are multiple types, do not memorize each type. . 2. Morphologic Feature: ‘Crumpled tissue paper’ cell 3. Genetics: Most common LSD; 1/15 Ashkenazi Jews are carriers for type I; More than 150 mutations identified of the Glucocerebrosidase gene on chromosome 1 |
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G. Spingolipidosis LSD: Neimann-Pick Disease
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1. Clinical:
a. Type A: infants, hepatosplenomegaly, vomiting, mental retardation and death by 2 years old. More common b. Type B: intermediate form c. Type C: Most common form; childhood, ataxia, hepatosplenomegaly, retardation and hepatitis 2. Morphologic feature: Neiman-Pick C (NPC) vacuolated cell (SLIDE 34) filled with microvesicular fat seen commonly in the liver and the spleen. 3. Genetics: Sphingomyelinase gene on chromosome 11; 1/1000 Ashkenazi Jews is carrier. |
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H.Mucopolysaccharidoses (MPSs) LSDs
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1. 6 subtypes of mucopolysaccharidoses
2. 1/25,000 births 3. Hurler syndrome (MPS Type I): severe, hepatosplenomegaly, coarse facies, mental and growth retardation, corneal clouding, death by 10-15 years of age due to ‘coronary artery disease’ 4. Hunter syndrome (MPS Type II): milder, no corneal clouding 5. Genetics: Iduronidase genes a. MPS I is autosomal recessive with a mutation of the iduronidase gene on chromosome 4 b. MPS II is X-linked NT Note: To help remember, Dr. McGoey suggested thinking Men like to Hunt more so Hunter’s is X-linked (men). 6. A student asked “Should these characteristics be present when they are very young or do they develop over time?” Dr. McGoey answered “Yes. You should see these characteristics the moment they are born. Even very experienced and practiced pediatricians miss the features, but they should be identifiable.” |
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XXIII. Other Autosomal Recessive Disorders
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A. Thalessemias
B. Usher syndrome 1. huge population of Cajun individuals with this disorder in Louisiana; deafness and blindness C. Zellweger Syndrome: hepatorenal involvement with an abnormal face |
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XXV. Incontinentia Pigmenti
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X linked Dominant
A. Scenario: “beautiful swirling hyperpigmentation” patterns, teeth abnormalities, and ataxia. B. Features: Abnormal skin pigmentation, Conical or missing teeth, Ocular, Neurologic, also can be mentally affected C. Genetics: Seen only in females; Heterozygote females only mildly affected; Affected females have many SAB (spontaneous abortions) |
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Duchenne Muscular Dystrophy
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X linked recessive
uses his hands to crawl up his legs (Gauer’s sign) 1. Progressive weakness and muscle atrophy 2. Pseudohypertrophy of the calf muscles 3. Wheelchair-bound by age 11 4. Death by age 25 due to respiratory and cardiac failure C. Genetics: 1. incidence: 1/3500 males 2. Dystrophin gene mutations a. Deletions most common b. 1/3 are new mutations (Exception: remember autosomal dominant disorders, normally have new mutations). 2/3 of the time it is transmitted from the mother. (NO MALE TO MALE TRANSMISSION). 3. Carrier females may be mildly affected most likely with cardiac symptoms (ex: cardiomyopathy, mitral valve prolapse) |
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XXVIII. Glucose-6-Phosphate Dehydrogenase Deficiency
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X linked recessive
B. Features: 1. Hemolytic anemia occurs in response to certain drugs, infections, foods (especially fava beans). 2. Anemia is self-limited 3. 10% of U. S. black males are affected (very common) C. Pathologic Feature: Heinz bodies in RBCs and bitocytes– the spleen removes the Heinz bodies and makes it seem as if the RBCs have been bitten into. D. Genetics: G6P dehydrogenase gene |
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XXIX. Hemophilia:
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X linked recessive
B. Feature: 1. Easy bruising, hemorrhage, hemarthroses (bleeding into the joint) 2. Subtype A worse than B C. Genetics: 1. Type A: factor VIII gene (Antihemophilic factor) (NT Note: A and Ate (8) – if that helps at all) 2. Type B: factor IX gene (Christmas factor) 3. 1/3 are new mutations; 2/3 are due from transmission from the mother 4. Carrier females are at risk for mild bleeding tendencies. Female teenagers tend to present with very heavy periods. |