Heritable disorders AB

Question 1

Peutz-Jeghers syndrome - mode of inheritance and genetic abnormality?

Answer 1

Autosomal dominant

Gene encodes serine threonine kinase LKB1 or STK11

Question 2

What percentage of patients with Peutz-Jeghers syndrome will have died from a related cancer by the age of 60 years?

Answer 2

50%

Question 3

What is the genetics of A1AT?

Answer 3

AR/codominant inheritance
Ch 14

PIMM = normal
PiSS homozygous = 50% normal A1AT
PiZZ homozygous = 10% normal A1AT

Question 4

Wilson’s disease - what is the mode of inheritance and gene involved?

Answer 4

Autosomal recessive

ATP7B on Ch 13

Question 5

Wilson’s disease - what are the LFT findings?

Answer 5

Elevated transaminases

DECREASED ALP as copper interferes with synthesis of ALP

Question 6

What are some clinical features of Wilson’s disease?

Answer 6

Hepatic - first sign in children
Psychiatric - speech and behaviour
Neurologic - dysarthria, ataxia, tremor, parkinsonism, dystonia 
Renal - RTA (esp Fanconi)
Eye - Kayser-Fleischer rings
Haemolysis
Blue nails

Question 7

What are the common neurologic manifestations of Wilson’s disease?

Answer 7

Dysarthria – majority
Gait abnormalities/ataxia
Dystonia 
Tremor 
Parkinsonism
Drooling

Question 8

What is the treatment of Wilson’s disease?

Answer 8

Chelating agents - Penicillamine, Trientine
New - Tetrathiomolybdate
Low copper diet