Gen and Cong Abnormalities Flashcards
mendelian disorder
single gene mutations
AD disorders
affects non-enzyme proteins
affects key structural proteins
AR disorder
largest category of mendelian disorders expression more uniform complete penetrance common loss of function of enzyme protein inborn errors of metab
X-linked disorders
recessive (almost all)
dominant –> Vit D -resistant rickets
Galactosemia
accumulation of substrate
Albinism
enzyme defect leading to metabolic block –> dec amount of end product
alpha-1-antitrypsin def
failure to inactivate tissue-damaging substrate
Familial Hypercholesterolemia
reduced synthesis or function of LDL receptors
most frequent mendelian disorder
Cystic fibrosis
defective system for Cl- xsport
Sickle cell disease
alter nonenzyme protein structure
Thalassemia
mutation in globin genes affect amount of globin chains synth
Osteogenesis imperfecta
collagen structural defect
Muscular dystrophy
Dystrophin structural defect
hereditary spherocytosis
spectrin structural defect
G6PD deficiency
gen determined adverse reaction to drugs (fava beans)
Marfan syndrome
fibrillin defect
arachnodactyly / lax joints / lens dislocation / mitral valve prolapse / aortic dissection and dilation
Ehlers-Danlos Syndrome
disorders of defective collagen synthesis or structure
hyper extensible skin / hyper mobile joints / colon rupture / artery rupture, etc
14 types
Tay-Sachs Disease
GM2 gangliosidosis Hexosaminidase A deficiency ganglioside accumulation in tissues chromosome 15 Oil red O stain cherry red spot in macula
Neimann-Pick Disease
accumulation of sphingomyelin sphingomyelinase def Type A most common --> severe infantile form lipid laden foam cells cherry red spot
most common lysosomal storage disease
Gaucher disease
Gaucher disease
most common lysosomal storage disease
glucocerebrosidase gene mutation
glucocerebroside accumulation in phagocytes –> Gaucher cells –> crumpled tissue paper (fibrillary cyto)
PAS+
Type I Gaucher disease
most common
limited to phagocytes throughout the body
spares CNS
Type II Gaucher disease
infantile acute cerebral pattern
die early
no predilection for Jews
Mucopolysaccharidoses
types I-IV
all are AR except Hunter (XR)
coarse facial features / cloudy cornea / stiff joints / mental retardation
Alkaptonuria (Ochronosis)
homogentisic oxidase def accumulation of homogentisic acid black urine upon standing black/blue discoloration of tissues degenerative arthropathy --> cart becomes brittle and fibrillated
neurofibromatosis type I
neurofibromas
cafe au lair spots
lisch nodules –> pigmented iris hamartomas
mutation NF-1 gene –> codes for neurofibromin (tumor suppressor gene)
neurofibromatosis type II
bilateral acoustic schwannomas
multiple meningiomas
NF-2 gene –> also tumor suppressor
Tuberous Sclerosis
AD
CNS hamartomas –> cortical tubers and subependymal nodules
other tumors
cutaneous lesions (ash-leaf patches and such)
TSC1 = hamartin mutation
TSC2 (more common) = tuber in mutation
proteins forms complex inhib the kinase mTOR
lots of cyto; giant cell astrocytomas in CNS and cardiac rhabdomyomas
Trisomy 21
Down Syndrome most common chromosomal disorder d/t meiotic disjunction maternal age strong influence simian crease / brushfield spots on iris / etc
Trisomy 18
Edwards syndrome overlapping fingers micrognathia low set ears rarely live more than a few years
Trisomy 13
Patau syndrome
cleft lip and palate
rocker-bottom feet
rarely live more than a few years
Principle cause of reduced spermatogenesis and male infertility
Klinefelter syndrome
XXY
most common sex abnormality in females
Turner syndrome
XO
cystic hygroma
Rubella
at risk first 16 wks
PDA
microcephaly
cataracts
most common fetal viral infection
CMV
highest risk period is second trimester
owl eye inclusions
