Blood

Question 1

Acute Intermittent Porphyria;

Answer 1

AD, HMBS
onset after puberty: acute attacks of abdominal pain, weakness, neuropathy, anxiety
No cutaneous findings
tx: stop precipitant, intubate if bulbar paralysis
FDA approved RNAito repress ALAS1 > reduce frequency

Question 2

Alpha thalassemias

Answer 2

-85% caused by deletions
–/++ is common in SE asian
Hb Barts (hydrops fetails)- 0 functional copies of Alpha, incompatible with life- y4 tetramers
Hb H- 1 functional copy- anemia + splenomegalyt
Alpha thal minor- 2 functional copies- mild anemia
Treatment: transfusions, supportive care

Question 3

Beta thalassemia:

Answer 3

HBB
Beta thal: 90% caused by recurrent SNVs
Major- pale, severe anemia> FTT, hepatosplenomegaly, jaundice
prominent facial bones b/c bone marrow expansion
Minor: mild anemia/asx
Treatment: transfusion + iron chelation> surivival beyond 30y

Question 4

ATRX-related alpha thalassemiax

Answer 4

XL, ATRX
Microcytic anemia/Hb H, ID, hypotonic facies,

Question 5

Sickle cell:

Answer 5

AR, HBB
E6V is common variant; dz arizes either when HOM or in trans w/ beta thal variant (null)
anemia, splenomegaly, FTT, swollen limbs, infarcts, high infection risk from aplenia
infection is leading cause of death
Het advantage- malaria. Unaffected mostly, but higher risk for rhabdomyolysis

Question 6

Von Willebrand Disease:

Answer 6

AD/AR, VWF
Type 1 (AD): most common inherited bleeding dx
Type 3 (AR): most severe
Mucocutaneous bleeding (ie superficial), bruising

Question 7

Hemophilia A & B:

Answer 7

XLR, F8 (hemophilia A), F9 (hemophilia B)
deep bleeds
often seen with cephalohemotomas, bleeding after circumcision
A: 20-50% of cases caused by intrachromosomal inversion (ex1-22) usually from male meisosis: severe
L1 inserstions also common in A
B: no recurrent variants
F9 leyden- promoter variants- severe hemophilia in childhood that resolves in puberty
Diagnosis: activated partial thromboplastin time test
Treatment: IV infusion of missing factor

Question 8

Factor V Leiden thrombophilia:

Answer 8

AD/AR, F5
risk of venous thromboembolism, mostly DVTs. Hets have modest riskk
arterial thrombosis, MI, and stroke not a/w F5
testing: Activated protein C,
Dx: F5 c.1691G>A (100%)

Question 9

Heriditary Hemochromotosis:

Answer 9

AR, HFE
high iron absorption> abdominal pain, weakness, lethargy, weight loss
C282Y Hom’s only
tx: phlebotomy

Question 10

XL agammaglobulinemia:

Answer 10

XLR, BTK
recurrent pneumonia, sinusitis, sepsis, meningitis

Question 11

Familial Mediterranean Fever;

Answer 11

AR, MEFV
Type1: recurrent febrile episodes w/ peritonitis, synovistis, erypsipelas-like erythrema, amyloidosis
favorable response to colchine
Type 2: amyloidosis is 1st presentation
M694V- treated w/ colchicine for life.