Lecture 8 - Genetic Disease presentations Flashcards
Waardenburg syndrome:
a group of syndromes that have problems with _____ and _____
auditory (deafness), hypopigmentation
waardenburg:
characteristic hypopigmentation of skin and _____, dystopia _____ in type 1;
type 2 doesn’t have _____ but increased risk hearing loss
forelock;
canthorum;
dystopia canthorum
waardenburg:
types 1-3 are inherited in an ____ ___ pattern. type 4 has a _____ _____ inheritance
autosomal dominant;
autosomal recessive
waardenburg:
genes implicated are involved in what cell line? (ie endoderm, mesoderm, neural crest);
neural crest
MITF, PAX3, SOX10
maple syrup urine disease (MSUD):
due to deficiency in _____, causing increased _____ in blood.
branched chain alpha keto acid dehydrogenase;
alpha ketoacids
MSUD:
causes severe ____ defects. urine smells like ______.
inheritance = _____;
seen in pennsylvania ____ population
CNS/birth;
maple syrup;
autosomal recessive;
mennonite
MSUD:
supplementation with ____ may help some patients;
avoid ____, ____, ____
thiamine;
isoleucine, leucine, valine
congenital adrenal hyperplasia (CAH):
inheritance = _____;
most common form is due to deficiency in ______
associated with CYP____ mutations
autosomal recessive;
21 hydroxylase;
21A2
CAH (21 hydroxylase deficiency):
____ mineralocorticoids, _____ cortisol, _____ sex hormones;
blood pressure is _____;
potassium is ____
decreased, decreased, increased
decreased, increased
CAH:
look for increased _____ in serum;
treat with ______ and mineralocorticoids;
presents as _____ in females
17-hydroxyprogesterone;
glucocorticoids;
virilization
Von hippel-Lindau disease (VHL)”
inheritance = _____;
due to VHL gene deletion on chromosome _____
VHL protein usually _____ its target protein HIF 1-alpha
autosomal dominant;
3;
ubiquinates
VHL:
mutation in VHL causes resistance of cells to ____ and stimulation of _____
hypoxia, angiogenesis
VHL: look for H = A = R = P =
hemangioblastomas (cerebellum, retina);
angiomatosis (hemangiomas in skin);
Renal cell carcinoma (bilateral);
Pheochromocytoma
Ehler’s danlos:
classic type is caused by a mutation in type ___ collagen due to mutations in ____ gene.
5;
COL5A1 or 2;
Autosomal dominant
Ehler’s danlos:
vascular type is due to mutation in type ____ collagen.
most common form is the _____ type
2;
hypermobility/hyper extensibility
hunter/hurler:
which one is autosomal recessive? which is X-recessive?
both have accumulation of _____ and _____
AR = hurler; XR = hunter;
heparan sulfate, dermatan sulfate
hunter/hurler:
deficiency of iduronate-2-sulfatase =
deficiency of alpha-L-iduronidase =
which is most severe?
iduronate - Hunter;
iduronidase - Hurler
hurler is bad
hunter/hurler: coarse facial features described as \_\_\_\_\_\_ like; corneal clouding in \_\_\_\_\_; intellectual disability in \_\_\_\_\_; hepatosplenomegaly in \_\_\_\_\_
gargoyle;
hurler;
hurler;
both
treatment for both hunter/hurler is _____ or _____
hematopoietic stem cell transplant;
enzyme replacement therapy
Medium-chain Acyl Dehydrogenase deficiency (MCAD):
inheritance = ______;
decreased ability to break down _____ into _____
autosomal recessive;
fatty acids, acetylCoa;
MCAD:
characterized by _____ _____ in blood;
patients must avoid _____;
presents as _____, ______, seizures, lethargy
hypoketotic hypoglycemia;
fasting;
vomiting, hepatomegaly
leber hereditary optic neuropathy:
inheritance = _____;
presents with blurring and clouding of _____ Vision;
more common in males, females, or equal?
mitochondrial;
central;
males
adrenoleukodystrophy:
inheritance = _____ ____;
disrupts metabolism of ______ in ______ (an organelle) due to impaired addition of ______
X-linked (usually recessive);
very long chain fatty acids, peroxisomes
coenzyme A
Adrenoleukodystrophy:
VLCFAs build up in ____, ____, and ____
nervous system, adrenal gland, testes
see adrenal/testicular atrophy, coma
