X-linked Recessive Disorders

Question 1

Lesch-Nyhan Syndrome

Answer 1

Mutated Gene: HPRT1, which produces Hypoxanthine phosphoribosyltransferase 1, which is used in the recycling of purines.

What are some clinical manifestation?

•Cognitive and behavioral disturbances
•Overproduction of uric acid
•Self injury

Question 2

What are Dystrophinopathies?

Answer 2

Gene mutated: DMD

Chromosome Xp21-21.1

•Dystrophin protein deficiency

•One of the largest human genes

Question 3

Duchenne Muscular Dystrophy

Answer 3

•What are the clinical manifestations of these disease?

–>Progressive muscular weakness proximal > distal
**Calf hypertrophy
**Dilated cardiomyopathy
**CK levels 10x normal
-Onset before the age of 5
-Wheelchair bound before 13
-Death in their 30’s
-Absence of Dystrophin, not even a little produced.

Question 4

Becker Muscular Dystrophy

Answer 4

What are some clinical signs?

Progressive muscular weakness proximal > distal
•Dilated cardiomyopathy
•CK levels 5x normal
•Later onset
•Wheelchair bound after 16
•Death in their 40’s
•Abnormal quantity or quality of Dystrophin (but present)

Question 5

DMD-associated DCM

Answer 5

•Dilated cardiomyopathy presenting between 20-40 years of age
•Early death
******No skeletal muscle involvement*****
•No Dystrophin in the myocardium

Question 6

Hemophilia A

Answer 6

Gene Mutated: F8 on Xq28, leads to a deficiency of Factor VIII

-22A inversion causes 50%

What is it?

Blood disorder where blood fails to clot appropriately due to a deficiency of Factor VIII

Clinical signs:
•Spontaneous bleeds into joints, muscles or intracranial
•Excessive bruising
•Prolonged bleeding after injury or incision
•Delayed wound healing