Lecture 8 - Genetic Disease presentations

Question 1

Waardenburg syndrome:

a group of syndromes that have problems with _____ and _____

Answer 1

auditory (deafness), hypopigmentation

Question 2

waardenburg:
characteristic hypopigmentation of skin and _____, dystopia _____ in type 1;
type 2 doesn’t have _____ but increased risk hearing loss

Answer 2

forelock;
canthorum;
dystopia canthorum

Question 3

waardenburg:

types 1-3 are inherited in an ____ ___ pattern. type 4 has a _____ _____ inheritance

Answer 3

autosomal dominant;

autosomal recessive

Question 4

waardenburg:

genes implicated are involved in what cell line? (ie endoderm, mesoderm, neural crest);

Answer 4

neural crest

MITF, PAX3, SOX10

Question 5

maple syrup urine disease (MSUD):

due to deficiency in _____, causing increased _____ in blood.

Answer 5

branched chain alpha keto acid dehydrogenase;

alpha ketoacids

Question 6

MSUD:
causes severe ____ defects. urine smells like ______.
inheritance = _____;
seen in pennsylvania ____ population

Answer 6

CNS/birth;
maple syrup;
autosomal recessive;
mennonite

Question 7

MSUD:
supplementation with ____ may help some patients;
avoid ____, ____, ____

Answer 7

thiamine;

isoleucine, leucine, valine

Question 8

congenital adrenal hyperplasia (CAH):
inheritance = _____;
most common form is due to deficiency in ______
associated with CYP____ mutations

Answer 8

autosomal recessive;
21 hydroxylase;
21A2

Question 9

CAH (21 hydroxylase deficiency):
____ mineralocorticoids, _____ cortisol, _____ sex hormones;
blood pressure is _____;
potassium is ____

Answer 9

decreased, decreased, increased

decreased, increased

Question 10

CAH:
look for increased _____ in serum;
treat with ______ and mineralocorticoids;
presents as _____ in females

Answer 10

17-hydroxyprogesterone;
glucocorticoids;
virilization

Question 11

Von hippel-Lindau disease (VHL)”
inheritance = _____;
due to VHL gene deletion on chromosome _____
VHL protein usually _____ its target protein HIF 1-alpha

Answer 11

autosomal dominant;
3;
ubiquinates

Question 12

VHL:

mutation in VHL causes resistance of cells to ____ and stimulation of _____

Answer 12

hypoxia, angiogenesis

Question 13

VHL:
look for 
H =
A =
R =
P =

Answer 13

hemangioblastomas (cerebellum, retina);
angiomatosis (hemangiomas in skin);
Renal cell carcinoma (bilateral);
Pheochromocytoma

Question 14

Ehler’s danlos:

classic type is caused by a mutation in type ___ collagen due to mutations in ____ gene.

Answer 14

5;
COL5A1 or 2;

Autosomal dominant

Question 15

Ehler’s danlos:
vascular type is due to mutation in type ____ collagen.

most common form is the _____ type

Answer 15

2;

hypermobility/hyper extensibility

Question 16

hunter/hurler:
which one is autosomal recessive? which is X-recessive?

both have accumulation of _____ and _____

Answer 16

AR = hurler;
XR = hunter;

heparan sulfate, dermatan sulfate

Question 17

hunter/hurler:

deficiency of iduronate-2-sulfatase =
deficiency of alpha-L-iduronidase =
which is most severe?

Answer 17

iduronate - Hunter;
iduronidase - Hurler

hurler is bad

Question 18

hunter/hurler:
coarse facial features described as \_\_\_\_\_\_ like;
corneal clouding in \_\_\_\_\_;
intellectual disability in \_\_\_\_\_;
hepatosplenomegaly in \_\_\_\_\_

Answer 18

gargoyle;
hurler;
hurler;
both

Question 19

treatment for both hunter/hurler is _____ or _____

Answer 19

hematopoietic stem cell transplant;

enzyme replacement therapy

Question 20

Medium-chain Acyl Dehydrogenase deficiency (MCAD):
inheritance = ______;
decreased ability to break down _____ into _____

Answer 20

autosomal recessive;

fatty acids, acetylCoa;

Question 21

MCAD:
characterized by _____ _____ in blood;
patients must avoid _____;
presents as _____, ______, seizures, lethargy

Answer 21

hypoketotic hypoglycemia;
fasting;
vomiting, hepatomegaly

Question 22

leber hereditary optic neuropathy:
inheritance = _____;
presents with blurring and clouding of _____ Vision;
more common in males, females, or equal?

Answer 22

mitochondrial;
central;
males

Question 23

adrenoleukodystrophy:
inheritance = _____ ____;
disrupts metabolism of ______ in ______ (an organelle) due to impaired addition of ______

Answer 23

X-linked (usually recessive);
very long chain fatty acids, peroxisomes
coenzyme A

Question 24

Adrenoleukodystrophy:

VLCFAs build up in ____, ____, and ____

Answer 24

nervous system, adrenal gland, testes

see adrenal/testicular atrophy, coma