Genetic Diseases II Flashcards
examples of autosomal recessive disorders
lysosomal storage disease
glycogen storage disease
alkaptonuria
characteristics of autosomal recessive disorders
uniform expression
complete penetrance
early onset
proteins show loss of function
what does alkaptonuria look like
black blue pigmentation
alkaptonuria is a defiency of waht
homogentisic acid oxidase
what is binding to collagen in alkaptonuria
homogentisitc acid
what does urine look like in alkaptonuria
turns black if allowed to stand and oxidize or if you add an alkali
what serious disease can alkaptonuria cause
degenerative arthropathy
degenerative arthropathy
like severe osteoarthiritis at an early age
what does alkaptonuria look like histologically
yellow-brown
what do lysosomal storage disease come from
failure of catabolism of large molecules within lyososmes
what are examples of lysosomal storage disease
tay sachs
gaucher
neimann pick
mucopolysaccharidoses
how do you treat lysosomal storage disease
enzyme replacement therapy
tay sachs is common in what population
ashkenazi jew
what is tay sachs caused by
framshift mutation in HexA gene
what does muation on HexA gene cause
lack of hexosaminidase A causing accumulation of GM2 ganglioside
what is seen in babies with tay sachs
seem normal but develop retardation and blidness, brain enlarges
when does death occur in tay sachs
before age 4
what does light microscopy show in tay sachs
pale, swollen (ballooned) neurons
what is a characteristic feature of tay sachs
cherry red spots
what is the most common lysosomal storgae disorder
gaucher
gaucher disease is caused by a mutation in what
gene encoding for enzyme beta-glucocerebrosidase on chromosome 1q
what is happening in gaucher diesae
you get an accumulation of macrophages and you can’t break down sugars
what are guacher cells
huge macrophages that are bloated with glucerebroside
where do gaucher cells accumulate
spleen, liver, and bone marrow
what do cells affected by gauche rlook like
wrinkled tissue paper/crinkled cigarette paper
what is the most common type of guacher
type I
type I guacher
adult
common in askenazi jews
compatitive with long healthy life
what are some common symptoms of gaucher
splenohepatomegaly
excruiting bone pain
type II guacher
severe
onset in first year of life
type III guacher
moderate to severe
onset in childhood
how do you test for guacher
bone marrow bipsy and aspiration to look for gaucher cells
how can you treat gauchers
imiglucerase
how can you treat gauchers
imiglucerase
nimann-pick disease is caused by a problem on what chromosome
11
type A niemann pick is what type of mutation
missense
what does the missense mutation in type A neimann pick cause
severe accumulation of spingomyelin, foamy cyptoplasm with zebra bodies
type C neimann pick is caused by
deficieny in cholersterol transport
type A and B neimann pick is caused by
defiency in sphingomyelinase
what are symptoms of neimann pick type A
neurologic signs
splenohepatomegally
enlarged lymph nodes
whare are symptoms of neimann pick type B
survive into adulthood
no CNS involvement
splenohepartomegay
what is the most common type of niemann pick disease
type C
neimann pick type C is caused by a mutation in
NPC1 and NPC2 genes
neimann pick type C causes a defect in what
nonenzymatic lipid trasport
what are symptoms of neimann pick type C
hydrop fetalis
neonatal hepatitis
chronic progressive neurological damge
what is the childhood presentatio nof neimann pick type C
atazia
dystonia
psychomotor deterioation
what are the disease that disprportionately affect ashkenzai jews
cystic fibrosis
gaucher
niemann-pick
tay sach
MPS
defiecnt lysosomal enzymes that degrade mucopolysacchraides
MPS 1-H (hurler syndrome)
most severe
defiency of alpha L iduronidase
MPS II (hunter syndrome)
milder
defiency of L-iduronidate sulfatase
where does MPS acculate
in lysosomes of RES and smooth muscle cells throughout the body
Sanfilippo
severe mental retardation, near normal looking
Morquio
dwarf, with bad aortic bales and normal IQ
how is hunter syndrome passed on
x-linked
what is the key sign of MPS
subendothelial arterial deposities - especially in coronary arteries
What are teh 3 glycogen storage diseases we need to know
von Gierke
Pompe
McArdle
pompe disease is also called
type II glycogenosis
what are problems assocaited with pompe disease
very compromised heart and skeletal muscle
progessie cardiomyopathy
massive cardiomegaly
infantile onset of pompe diseas look like
floppy baby
big tongue
von gierke disease
defiency glucose 6 phosphates
what are the symptoms of von gierke disease
hepatomegaly
hypoglycemia
gout
convusions
mcardle syndrome
defiencent muscle glycogen phosphrylase
