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75 Cards in this Set
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- 3rd side (hint)
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Achondroplasia
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AD
cell-signalling defect FGF receptor 3 |
dwarfism
advanced paternal age |
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ADPKD
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AD
APKD1 on chromosome 16 |
bilateral
berry aneurysm MVP adult form |
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FAP
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AD
APC gene on chromosome 5q two hit hypothesis |
colon cancer
adenomatous polyps after puberty pancolonic; almost always involves rectum |
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Familial hypercholesterolemia (hyperlipidemia type IIA)
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AD
defective/absent LDL receptor |
heterozygotes: cholesterol 300
homozygotes: cholesterol 700+, MI before 20 yo, tendon xanthomas |
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Hereditary hemorrhagic telangiectasia/Osler-Weber-Rendu
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AD
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telangiectasia, recurrent epistaxis, skin discolorations, AVMs
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Hereditary spherocytosis
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AD
spectrin/ankyrin defect |
Hemolytic anemia
increased MCHC cure w/splenectomy positive osmotic fragility test |
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Huntington's
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AD
Chromosome 4 trinucleotide repeat--CAG |
decreased GABA and ACh in the brain
anticipation |
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Marfan's
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AD
Fibrillin |
CT disorder
pectus excavatum cystic medial necrosis of aorta-->dissecting aortic aneurysm floppy MV subluxation of lenses |
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MEN 1, 2A, 2B
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AD
MEN 2A, 2B: ret gene |
familial endocrine tumors
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Neurofibromatosis type 1/von Recklinghausen's
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AD
long arm of chromosome 17 |
cafe-au-lait spots
neural tumors Lisch nodules skeletal disorders optic pathway gliomas |
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Neurofibromatosis type 2
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AD
NF2 gene on chromosome 22 |
juvenile cataracts
bilateral acoustic schwannomas |
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Tuberous sclerosis
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AD
Incomplete penetrance |
ash leaf spots
cortical/retinal hamartomas seizures MR renal cysts/angiomyolipomas cardiac rhabdomyomas astrocytomas |
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von Hippel-Lindau
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AD
deletion of VHL (tumor suppressor) on chromosome 3p-->constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors |
hemangioblastomas of retina/cerebellum/medulla
multiple bilateral renal cell carcinomas and other tumors |
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albinism
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variable inheritance due to locus heterogeneity
tyrosinase deficiency: AR defective tyrosine transporters: variable |
lack of neural crest cell migration
increase risk of skin cancer decreased ability to synthesize melanin from tyrosine or decreased tyrosine available for melanin synthesis |
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ARPKD
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AR
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infantile polycystic kidney disease
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Cystic fibrosis
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AR
CFTR gene on chromosome 7 deletion of Phe 508 defective Cl- channel |
most common lethal genetic disease of caucasians
fat soluble vitamin def male infertility failure to thrive pseudomonas/staph aureus pulmonary infections chloride sweat test |
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hemochromatosis
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AR
HLA-A3 association |
micronodular cirrhosis + DM + skin pigmentation = bronze diabetes
CHF increased risk of hepatocellular carcinoma sets off metal detectors treat w/ phlebotomy, deferoxamine |
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Bruton's aggamaglobulinemia
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XR
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--
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Wiskott-Aldrich Syndrome
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XR
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--
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Fabry's
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XR
alpha-galactosidase A deficiency |
ceramide trihexoside accumulates
peripheral neuropathy angiokeratomas CV/renal disease |
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G6PD
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XR
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most common human enzyme deficiency
more common in blacks (malarial resistance) decreased NADPH in RBCs-->hemolytic anemia bite cells Heinz bodies |
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Ocular albinism
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XR
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--
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Lesch-Nyhan syndrome
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XR
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--
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Hunter's syndrome
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XR
Iduronate sulfatase deficiency |
heparan sulfate, dermatan sulfate accumulate
mild Hurler's + aggressive behavior NO corneal clouding |
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Hemophilia A
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XR
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--
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Hemophilia B
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XR
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--
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Duchenne's
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XR
frame-shift mutation--.deletion of dystrophin gene (DMD) DMD=longest known human gene-->increased rate of spontaneous mutation |
weakness beginning in pelvic girdle, progresses superiorly
calf pseudohypertrophy Gower's maneuver cardiac myopathy onset before 5 yo |
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Becker's
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XR
dystrophin gene (DMD) |
less severe than Duchenne's
onset adolescence/early adulthood |
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Fragile X
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X-linked mutation
affects methylation and expression of FMR1 gene chromosomal breakage trinucleotide repeat--CGG |
2nd most common cause of genetic MR
large testes, jaw, ears autism MVP |
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Down syndrome
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trisomy 21
95%: meiotic non-disjunction of homologous chromosomes 4%: Robertsonian translocation 1%: mosaicism (no maternal association) |
most common chromosomal d/o
most common cause of congenital MR advanced maternal age MR, flat facies, epicanthal folds, simian crease, duodenal atresia, septum primum-type ASD, increased risk ALL and early Alzheimer's |
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Edwards' syndrome
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Trisomy 18
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most common trisomy-->live birth after Down's
MR, rockerbottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease death usually within 1 year |
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Patau's syndrome
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Trisomy 13
May be due to Robertsonian translocation |
severe MR, rocker bottom feet, micropthalmia, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart diease
death usually within 1 year. |
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Cri-du-chat
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microdeletion of short arm of chromosome 5
46, XX or XY, 5p- |
high pitched "mewing"
microcephaly MR epicanthal folds cardiac abnormalities |
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Williams syndrome
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microdeletion of long arm of chromosome 7
deleted region includes elastin gene |
elfin facies
MR hypercalcemia/increased sensitivity to vitamin D well-developed verbal skills extreme friendliness with strangers cardiovascular problems |
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DiGeorge syndrome
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22q11 deletion
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thymic, parathyroid, cardiac defects
aberrant development of 3rd and 4th branchial pouches |
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Velocardiofacial syndrome
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22q11 deletion
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palate, facial, and cardiac defects
aberrant development of 3rd and 4th branchial pouches |
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Essential fructosuria
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AR
fructokinase defect |
benign, asymptomatic
fructose appears in blood and urine |
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fructose intolerance
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AR
aldolase B deficiency |
fructose-1-phosphate accumulates-->decrease in available phosphate-->inhibition of glycogenolysis and gluconeogenesis
hypoglycemia, jaundice, cirrhosis, vomiting limit fructose and sucrose |
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galactokinase deficiency
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AR
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mild
galactitol infantile cataracts failure to track objects/develop a social smile |
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classic galactosemia
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AR
absence of galactose-1-phosphate uridyltransferase |
galactitol
failure to thrive, jaundice, hepatosplenomegaly, infantile cataracts, mental retardation exclude galactose and lactose from diet |
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ornithine transcarbamoylase (OTC) deficiency
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XR
other urea cycle enzyme deficiencies are AR |
orotic acid
hyperammonemia decreased BUN |
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PKU
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AR
decreased phenylalanine hydroxylase OR tetrahydrobiopterin cofactor |
tyrosine is essential
screen at birth MR growth retardation seizures fair skin, eczema musty body odor limit phenylalanine and increase tyrosine in diet d/o of aromatic amino acid metabolism |
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alkaptonuria
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AR
homogentistic acid oxidase deficiency |
dark connective tissue
brown sclera black urine benign |
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cystinuria
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AR
defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in the PCT |
cystine staghorn calculi
acetazolamide to alkalinize the urine fairly common |
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maple syrup urine disease
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decreased alpha-ketoacid dehydrogenase
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blocked degradation of branched amino acids
urine smells like maple syrup severe CNS defects, death |
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Hartnup disease
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AR
defective neutral aa transporter on renal and instestinal epithelial cells |
urinary tryptophan excretion
decreased gut tryptophan absorption pellagra |
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homocystinuria
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AR
1. cystathionine synthase deficiency 2. decreased affinity of cystathionine synthase for pyridoxal phosphate 3. homocysteine methyltransferase deficiency |
cysteine is essential
MR osteoporosis, tall stature, kyphosis downward and inward lens subluxation atherosclerosis |
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Von Gierke's disease (type 1 glycogen storage disease)
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AR
glucose-6-phosphatase deficiency |
severe fasting hypoglycemia
increased liver glycogen increased blood lactate hepatomegaly |
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Pompe's disease (type 2 glycogen storage disease)
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AR
lysosomal alpha-1,4-glucosidase (acid maltase) |
"trashes the pump": heart, liver, muscle
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Cori's disease (type 3 glycogen storage disease)
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AR
debranching enzyme (alpha-1,6-glucosidase) |
milder form of von Gierke's/type 1 with normal blood lactate levels
gluconeogenesis is intact |
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McArdle's (type 5 glycogen storage disease)
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AR
skeletal muscle glycogen phosphorylase |
increased glycogen in muscle
painful muscle cramps myoglobinuria w/strenuous exercise |
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Gaucher's disease
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AR
beta-glucocerebrosidase deficiency |
glucocerebroside accumulates
Ashkenazi (sometimes) hepatosplenomegaly bone crises macrophages=crumpled tissue paper aseptic necrosis of femur sphingolipidosis |
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Niemann-Pick disease
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AR
sphingomyelinase deficiency |
sphingomyelin accumulates
Ashkenazi cherry red spot on macula foam cells hepatosplenomegaly (vs none in Tay-Sachs) sphingolipidosis |
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Tay-Sachs disease
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AR
hexosaminidase A deficiency |
GM2 gangloside accumulates
Ashkenazi cherry red spot on macula lysosomes with onion skin NO hepatosplenomegaly (vs Niemann-Pick) sphingolipidosis |
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Krabbe's disease
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AR
galactocerebrosidase deficiency |
galactocerebroside accumulates
peripheral neuropathy, developmental delay optic atrophy globoid cells |
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metachromatic leukodystrophy
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AR
arylsulfatase A deficiency |
cerebroside sulfate accumulates
central and peripheral demyelination ataxia + dementia sphingolipidosis |
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Hurler's syndrome
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AR
alpha-L-iduronidase deficiency |
Heparan sulfate, dermatan sulfate accumulate
gargoylism airway obstruction corneal clouding mucopolysaccharidosis |
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Abetalipoproteinemia
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AR
deficiencies in apoB-100 and apoB-48 |
unable to synthesize lipoproteins
first few months of life steatorrhea acanthocytosis ataxia night blindness lipid accumulation in intestinal enterocytes |
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Bruton's agamaglobulinemia
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XR
defect in BTK (tyrosine kinase gene) |
blocks B-cell differentiation/maturation
recurrent bacterial infections after 6 mos of age labs: normal pro-B, decreased maturation, number of B cells, all classes of immunoglobulines |
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SCID (Severe combined immunodeficiency
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X-linked most common: IL-2 receptor defective
also: adenosine deaminase deficiency, failure to synthesize MHC II antigens |
B and T cell deficiencies
recurrent viral, bacterial, fungal, and protozoal infections treat w/bone marrow transplant; no allograft rejection labs: decreased IL-2R; increased adenine (toxic to T and B cells); decreased dNTPs, decreased DNA synthesis |
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Chediak Higashi syndrome
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AR
defect in microtubular function |
defect-->decreased phagocytosis
recurrent pyogenic infections by staph and strep partial albinism peripheral neuropathy |
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Wiskott-Aldrich syndrome
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XR
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Progressive deletion of B and T cells
TIE: thrombocytopenic purpura, infections, eczema labs: increased IgE, IgA; decreased IgM |
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ataxia telangiectasia
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AR
ATM gene, chromosome 11 defect in DNA repair enzymes |
triad of ataxia, telangiectasia, and IgA deficiency
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Peutz-Jegher's syndrome
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AD
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multiple nonmalignant hamartomas throughout GI tract
hyperpigmented mouth, lips, hands, genitalia increased risk of CRC/visceral malignancies |
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HNPCC: Hereditary nonpolyposis colorectal cancer/Lynch syndrome
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AD
mutation of DNA mismatch repair genes |
80% progress to CRC
proximal colon always involved |
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Alpha1-antitrypsin deficiency
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codominant
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misfolded gene product accumulates in hepatocellular ER
panacinar emphysema PAS + globules in teh liver |
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Wilson's disease
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AR
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asterixis
basal ganglia degeneration (parkinsonism) ceruloplasmin decreased, cirrhosis copper accumulation, hepatocellular carcinoma dementia, dyskinsesia, dysarthria hemolytic anemia Kayser-Fleischer rings penicillamine to treat |
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alpha-thalassemia
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alpha-globin gene mutations-->decreased synthesis
deletion 4 gene deletion: Hb Barts-->hydrops fetalis 3 gene deletion: HbH disease 1 or 2 gene deletion: no significant disease |
Asian and African populations
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beta-thalassemia
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point mutation in splicing sites and promoter sequences
minor: beta chain underproduced, asymptomatic heterozygote major: beta chain is absent, symptomatic homozygote |
both increased HbF
minor usually asymptomatic major: severe anemia, marrow expansion, crew cut xray, chipmunk facies, skeletal deformities Mediterranean populations |
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Sideroblastic anemia
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XR
defect in delta-aminolevulinic acid synthase gene |
defective heme synthesis
ringed sideroblasts increased iron and ferritin, normal TIBC treat w/pyroxidine (B6) |
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Sickle cell anemia
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point mutation
substitution of normal glutamic acid with valine at position 6 in the beta chain |
heterozygotes: resist malaria
homozygotes: aplastic crisis, autosplenectomy, salmonella osteomyelitis, renal papillary necrosis, splenic sequestration crisis crewcut skull xray sickled RBCs African |
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HbC
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point mutation
glutamic acid to lysine at position 6 of beta chain |
disease similar to but milder than sickle cell
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pyruvate kinase deficiency
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AR
defect in pyruvate kinase |
defect-->decreased ATP-->rigid RBCs
hemolytic anemia in a newborn |
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acute intermittent porphyria
|
AD
defect in porphobilinogen deaminase |
porphobilinogen, delta-ALA, and uroporphyrin accumulate
painful abdomen red urine polyneuropathy psych disturbances precipitated by drugs treat with glucose and heme |
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porphyria cutanea tarda
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AD
uroporphyrinogen decarboxylase |
uroporphyrin accumulates-->tea colored urine
blistering cutaneous photosensitivity most common porphyria |
