复旦大学：《医学遗传学 Medical Genetics》课程教学资源（学习报告）wilson's disease

Wilsons disease Heptolenticular Degeneration By Toni Ajoje-12301016001

Wilson’s Disease Heptolenticular Degeneration By Toni Ajoje - 12301016001

Wilsons disease Rare autosomal recessive disease Mutation of Wilson disease protein gene(atP7B) Excessive Copper accumulation in the liver or brain Leads to hepatitis Psychiatric or neurological symptoms Affects 1-4 out 100,000 people Fatal disease if not diagnosed early Disease usually manifest between ages 4 and late teens

Wilson’s Disease • Rare Autosomal recessive disease • Mutation of Wilson disease protein gene (ATP7B) • Excessive Copper accumulation in the liver or brain • Leads to Hepatitis, Psychiatric or Neurological symptoms • Affects 1-4 out 100,000 people • Fatal disease if not diagnosed early • Disease usually manifest between ages 4 and late teens

Discovery First described in 1912 by a british neurologist Samuel Alexander Kinnier Wilson(1878-1937)

Discovery • First described in 1912 by a British neurologist Samuel Alexander Kinnier Wilson (1878-1937)

Copper in the body Copper is as essential as any other vitamins and is present in most food Required by the body for different functions Most people have more cooper than they need, healthy people are able to excrete copper At birth people with Wilson's disease begin to accumulate copper and are unable to excrete it

Copper in the body • Copper is as essential as any other vitamins and is present in most food • Required by the body for different functions • Most people have more cooper than they need, healthy people are able to excrete copper • At birth people with Wilson’s disease begin to accumulate copper and are unable to excrete it

Copper in the body Copper is utilized as a cofactor for different enzymes such as Cerloplasmin and cytochrome C Copper membrane transporter 1(CMT1 carries copper into the cells Binds to a protein known as atoX1 in golgi apparatus

Copper in the body • Copper is utilized as a cofactor for different enzymes such as Cerloplasmin and cytochrome C • Copper membrane transporter 1(CMT1) carries copper into the cells. • Binds to a protein known as ATOX1 in golgi apparatus

Copper in the Liver-ATP7B Increasing levels of copper causes atP7A(an enzyme to release copper into portal vein to the Liver ATP7B binds copper to Cerluplasmin in the liver and releases it into the blood stream ATP7B also removes excess copper into bile Mutation of ATP7B in Wilson's disease impairs these functions

Copper in the Liver – ATP7B • Increasing levels of copper causes ATP7A (an enzyme) to release copper into portal vein to the Liver • ATP7B binds copper to Cerluplasmin in the liver and releases it into the blood stream • ATP7B also removes excess copper into bile • Mutation of ATP7B in Wilson’s disease impairs these functions

Copper metabolism Oral intake CMT 1 A01 ATP7A Tan多 Golgi netw ork CTGN tTrans-solgi netw ork Enterocyte Portal vein CuT 1 Nucleus AT Ox E LT B rans solg network (TN [Trans olgi network He patocte

Copper metabolism

Impairment of atP7B Impairment of aTP7B causes copper to accumulate in the liver-(it does not bind to cerluoplasmin) High levels of copper in the liver causes oxidative damage through a process known as Fentons Chemistry Oxidative damage in the liver leads to chronic Active Hepatitis

Impairment of ATP7B • Impairment of ATP7B causes copper to accumulate in the liver – (it does not bind to cerluoplasmin) • High levels of copper in the liver causes oxidative damage through a process known as Fenton’s Chemistry • Oxidative damage in the liver leads to Chronic Active Hepatitis

Impairment of atP7B Unbound copper is released into the bloodstream and deposits at different organs such as Kidney Eves Brain

Impairment of ATP7B • Unbound copper is released into the bloodstream and deposits at different organs such as • Kidney • Eyes • Brain

Copper in the brain Basal Ganglia and Related Structures of the Brain Copper is deposited in the basal ganglion and the Putamen These structures plays a role basal ganglIa in coordination of globus pallidus thalamus movement and mood substantia nigra regulation cerebellum

Copper in the Brain • Copper is deposited in the basal ganglion and the Putamen. • These structures plays a role in coordination of movement and mood regulation