Rapid Review 4 Flashcards
type 1 Crigler-Najjar has *** UGT activity
has NO UGT activity
type 2 Crigler-Najjar has *** UGT activity
has SOME/REDUCED UGT activity
how do Gilbert and Crigler-Najjar bilirubin levels compare?
Gilbert: only slightly increased (3-6)
CN type 1: highest bili (>20)
CN type 2: intermediate (5-20)
(unconjungated bili)
pure red cell aplasia is a paraneoplastic syndrome related to what tumor?
thymoma
what mutation is associated with AML with maturation?
t(6;9) DEK-NUP214
[you have to be ~mature to do 69]
what labs favor cholestatic overr hepatocellular jaundice?
alk phos >>> transaminases
cirrhosis SPEP characteristics
beta-gamma bridging & low albumin
broadly, which method do you use for hematocrit?
conductometry
TTP is an auto-Ab to what
ADAMTS13
what blood product should you use in TTP?
cryo-poor plasma
why should you use ~this blood product~ in TTP?
cryo-poor plasma
bc it has ADAMTS13 (vWF-cleaving metalloprotease)
which worm is a/w megaloblastic anemia?
diphyllobothrium latum
CD markers in
T-ALL vs ATLL
T-ALL: CD4+/8+ sCD3-/cCD3+ [4 & 8 double positive makes it TALLer]
ATLL: CD4+/8- CD3+ popcorn cells [eating popcorn 43 times in atlanta]
mutation in Langer-Giedion
del8q24
what level of sweat chloride is suggestive of cystic fibrosis?
>60 mmol/L
mutation in Wilson disease
ATP7B
what is the gold standard for diagnosing Wilson disease?
elevated hepatic copper
are these low or high in Wilson disease?
ceruloplasmin
urinary copper excretion
LOW ceruloplasmin (can appear normal d/t inflammatory states [APR]) HIGH urinary copper excretion
what pathway does Cowden syndrome impact?
mTOR pathway (PTEN in 85%, PIK3CA, AKT1)
inheritance of Cowden syndrome
auto DOMINANT
inheritance of Peutz-Jeghers syndrome
auto DOMINANT
mutation in Hartnup disease
SLC6A19
auto recessive
what’s the specific weird lab value in Hartnup?
increased urinary tryptophan
what is the problem in PKU/phenylkaptonuria?
phenylalanine hydroxylase deficiency
auto recessive mut in PAH gene on chrom 12
what is the problem in benign hyperphenylalaninemia?
deficiency of pterin-4a-carbinolamine dehydratase (altered BH4 cofactor)
what is the inheritance of ornithine transcarbamylase deficiency?
x-linked recessive
(complete or partial lack of ornithine transcarbamylase)
[urea cycle]
what is the problem in maple syrup urine disease?
BCKD deficiency: branched chain keto acid dehydrogenase
genes: BCKDHA, BCKDHB, DBT
auto recessive
what amino acids does BCKD break down?
leucine
isoleucine
valine
(LIV)
what is the deficiency in tyrosinemia type I?
fumarylacetoacetate hydrolase (FAH) deficiency
last step in tyrosine breakdown
what is the inheritance of tyrosinemia type I?
auto recessive
how do you diagnose tyrosinemia type I?
elevated succinylacetone in urine
what malignancy is tyrosinemia type I a/w?
HCC
what is the disease with “sweaty feet” odor?
isovaleric acidemia :(
what is the problem in isovaleric acidemia?
isovaleryl-CoA dehydrogenase deficiency
what is the disease with “boiled cabbage” odor + fetid breath?
hypermethioninemia
what is the issue in hypermethioninemia?
methionine adenosyltransferase deficiency (buildup of methionine > demyelination)
what is the disease that is aka fish-odor disease?
trimethylaminuria
what is the issue in trimethylaminuria/fish odor disease?
mutations in flavin monooxygenase 3 (FMO3) gene
buildup of trimethylamine
aka fish odor disease
Fish odor - Flavin monooxygenase
what is the mutation in hyperhomocysteinemia?
C677T mut in MTHFR [methylene tetrahydrofolate reductase]
which inborn error of metabolism is a/w an increased risk of thrombotic disorders?
hyperhomocysteinemia > elevated homocysteine causes endothelial cell toxicity and disrupted vascular hemostatic mechanisms
what are the 3 peroxisome biogenesis disorders, in order of severity?
least bad: Refsum disease (PHYH mut)
middle bad: neonatal adrenoleukodystrophy (ABCD1 mut)
worst: Zellweger syndrome (PEX mut)
which peroxisome biogenesis disorder can be treated with diet?
Refsum disesase
which peroxisome biogenesis disorder is a/w Leydig cell damage?
neonatal adrenoleukodystrophy
what is like, the core issue in peroxisome biogenesis disorders?
buildup of very long chain fatty acids (Refsum is phytanic acid specifically)
what is the mode of inheritance of the glycogen storage diseases?
all are auto recessive EXCEPT
TYPE IXa
what’s the eponym
type I GSD
von Gierke’s
what’s the deficiency
type I GSD
G6PC mut > glucose-6-phosphatase deficiency
what will TTP look like on a vWF gel?
increased high-molecular-weight multimers
vWD 2M
decreased ability of vWF to bind to GPIb receptor on plt (this is the opposite of 2B)
normal multimers on gel
vWD 2N
mutated vWF-factor VIII binding site > vWF can’t protect factor VIII from degradation (increased factor VIII clearance) > factor VIII levels fall
normal multimers on gel
vWD 2A
small, less active vWF bc large multimers can’t assemble
No HMWM or IMWM
only has LMWM on gel
vWD 2B
increased affinity of vWF for plt GPIb/V/IX (on plt) > rapid vWF clearance & low plts (this is the opposite of 2M)
No HMWM
Has IMWM and LMWM on gel
vWD type 3
NO vWF!
gel has an empty lane
which von willebrand disease types are quantitative?
type 1 and type 3
which von willebrand disease types are qualitative?
type 2A, 2B, 2M, 2N
which vWD can you NOT give DDAVP to?
type 2B
2B has increased affinity btwn vWF and GPIb > so you’ll just keep using up all your plts and worsen thrombocytopenia
what makes vWF?
endothelial cells & megakaryocytes
where is vWF stored?
endothelial cell: Weibel-Palade bodies
plts: alpha granules
3 normal functions of vWF
- bind to collagen + plt GPIb/V/IX complex > plt adhesion
- bind to plt GPIIb/IIIa > increased plt aggregation
- bind to FVIII > prolong half-life of FVIII
what is the gold standard for measuring vWF activity?
vWF:RCo
asks “how well does vWF agglutinate plts in response to ristocetin?”
what does vWF:Ag test?
measures amount of vWF present, via LIA or ELISA
what should you suspect if vWF activity (vWF:RCo) is decreased out of proportion to the decrease in vWF:Ag?
so RCo/Ag <0.5-0.7
type 2 vWD (esp 2A, 2B, 2M)
which vWD are auto recessive?
2N and 3
which vWD are auto DOMINANT?
1, 2A, 2B, 2M
what chromosome is the vWF gene on?
chromosome 12
what should you be thinking of if they give you a child with an abdominal mass and like, flow?
Burkitt
***multiple nucleoli, vacuolated cytoplasm***
CD19/20+, but also CD10+!!!
which glycogen storage disease is the most common one?
type I: von Gierke’s
which glycogen storage disease is the most severe?
type II: Pompe’s
what’s the eponym for type II glycogen storage disease?
Pompe’s
(pompeii has 2 ii’s)
what is the defect in Pompe’s?
alpha-1,4 glucosidase deficiency
aka
acid maltase deficiency
what’s the eponym for type III glycogen storage disease?
Cori’s/Forbes
what’s the defect in Cori’s/Forbes?
debranching enzyme deficiency
AGL mutation
(ABCD: andersen’s branching cori debranching)
what’s the eponym for type IV glycogen storage disease?
Andersen’s
what’s the defect in Andersen’s?
branching enzyme deficiency
(ABCD: andersen branching, cori debranching)
GBEI mutation
what is the eponym for type V glycogen storage disease?
McArdle’s
(ardle has 5 letters)
what’s the defect in McArdle’s?
muscle phosphorylase deficiency
(think of the IHC duh)
what’s the eponym for type VI glycogen storage disease?
Hers’
what’s the defect in Hers’ dz?
liver phosphorylase deficiency
PHKA2 mutation
what’s the eponym for type VII glycogen storage disease?
Tarui/Tauri
what’s the defect in Tarui’s?
muscle phosphofructokinase (pfk)
(causes deficiency of M subunit > myocytes & rbcs can’t use carbs for energy)