Heart Metal Transport Defects Flashcards
heavy metal transport defects discussed in this class
Hereditary hemochromatosis
Menkes Disease
Wilson Disease
disease that deals with IRON transport
hereditary hemochromatosis
disease that deals with COPPER transport
makes disease
wilson disease
hereditary hemochromatosis
inheritance and incidence
autosomal recessive
high incidence rate (very common)
hereditary hemochromatosis
genetic abnormality
caused by mutation on HFE gene on chromosome 6
missense mutation where try replaces cys
hereditary hemochromatosis
enzyme affected
HFE gene codes for a cell surface protein product that binds the transferrin
hereditary hemochromatosis
effect on substrate/byproduct
excess iron stored in multiple organs
hereditary hemochromatosis
pathophysiology
switch of cys with tyr affects how HFE protein interacts with transferrin receptor (which plays an imp. role in iron iron homeostasis)
HFE disrupts the intestinal cell’s ability to sense iron levels causing excessive absorption from small intestine –> iron overload (DOES NOT involve transport)
increasing intracellular iron causes per oxidative injury inducing degeneration, cell death, and fibrosis formation
hereditary hemochromatosis
clincial manifestation
excess iron stored in multiple organs (pleiotropic)
mc sign is cirrhosis of liver (jaundice)
cardiomyopathy, skin pigmentation, fatigue, and arthritis
classic symptom: Bronze skin
hereditary hemochromatosis
expression, penetrance
delayed onset (earlier for males than females due to menses)
NOT expressed in infancy
hereditary hemochromatosis
treatment
phlebotomy
may take years to deplete the storage
menkes disease inheritance
x-linked
neurodegenerative disease of impaired COPPER transport
menkes disease is of which element?
copper
menkes genetic abnormality
Menkes gene (ATP7A) in Xq13.3
deletion in large segments = FRAMESHIFT
menkes enzyme affected
protein responsible for copper transport and metabolism
menkes effect on substrate or byproduct
normally keeps copper concentration low in cells SO will have high copper concentrations
menkes pahophys
copper accumulation at LOW levels in liver, plasma, brain
higher than normal levels in kidneys and intestinal lining
menkes clinical manifestations
neonates: hypothermia, hypoglycemia, jaundice, umbilical hernias, unusual hair pigmentation
2-2.5 months is when parents notice
development of progressive hypotonia (limp)
coarse wiry hair by 4-5 months
menkes treatment
must be detected early before irreparable neurodegeneration occurs
bypass block in intestinal absorption of copper
copper replacement therapy
wilson disease v. menkes gene
ATP7 for both, B in wilson, A in menkes
Wilson Dz
genetic abnormality
mutation on ATP7B on chromosome 13
Wilson Dz
enzyme affected
P type ATPase
Wilson Dz
effect on substrate/byproduce
copper accumulation and toxicity to liver, brain, and eyes
Wilson Dz
clinical manifestation
copper accumulation begins at birth, symptoms of disorder don’t appear until later in life
KAYSER FLEISHCER RING
Kayser Fleischer ring
pathognomonic for wilson disease
deep copper colored ring at periphery of cornea
represents copper deposits
Wilson Dz
treatment
requires lifelong tx w/ various copper chelating meds to remove excess copper form body (low copper diet)
