Inherited Blood and Iron Disorders

Question 1

What is the difference between retrovirus vs. nonviral vector for gene therapy in patients with inherited diseases (e.g. hemophilia B)

Answer 1

Retroviruses have a preferred insertion site in the genome that is within oncogenes that can lead to development of leukemia later on.
Non-viral vectors use patient’s own fibroblasts. No oncogene risk but risk that the transduced gene will not persist

Question 2

What causes neurotoxicity in porphyrias

Answer 2

accumulation of ALA which interacts with gamma-aminobutyric acid nerve endings

Question 3

Genetic Defect in acute intermittent porphyria

Answer 3

PBG-deaminase gene defect leading to deficiency of hydroxymethylbilane synthas

Question 4

27 yo woman presents with abdominal pain, constipation, nausea, vomiting and hyponatremia. Only medication is OCP. Urine has dark red color
Diagnosis:
Diagnostic Test:

Answer 4

Diagnosis: Acute intermittent porphyria
Test: Elevated 24H urine ALA and porphobilinogen during crisis. Confirmed by RBC PBG deaminase activity <50%

Question 5

30 yo woman presents with blistering skin lesions, psych issues, and chronic abdominal pain.
Diagnosis:
Diagnostic Test:

Answer 5

Diagnosis: Variegate Porphyria
Test: STOOL protoporphyrin decreased. This is due to deficiency of protoporphyrinogen oxidase

Question 6

How do you treat neurovisceral crisis in porphyria?

Answer 6

Caloric loading dextrose 500 g daily.
Hemin if complicated by respiratory symptoms/failure
IVF

Question 7

Complications of Hemin (2)

Answer 7

DIC

Renal Failure

Question 8

50 yo man with blistering skin lesions in hands and other sun exposed areas and no abdominal pain.
Diagnosis:
Viral Association:

Answer 8

Diagnosis: Porphyria Cutanea Tarda

A/w Hepatitis C

Question 9

Enzyme deficiency that causes PCT?

Answer 9

uroporphyrinogen III decarboxylase

Question 10

8 yo boy with short stature, vertebral fractures, brown teeth and disgifuring photodermatitis. Diagnosis:
Enzyme Deficiency:

Answer 10

Congenital Erythropoietic Porphyria

Uroporphyrin III synthetase

Question 11

15 yo man presents with photosensitivity and chronic skin scarring. Family members similarly effected
Diagnosis:
Enzyme Deficiency:

Answer 11

Erythropoietic Protoporphyria

Ferrochelatase

Question 12

What happens to hepcidin in iron deficiency

Answer 12

Goes down

Question 13

What is the hepcidin level in hereditary hemochromatosis

Answer 13

LOW. This is what leads to iron overload

Question 14

Patient presents with elevated iron level, normal transferrin saturation and neurologic deficits. Diagnosis:
Pathophys:

Answer 14

Aceruloplasminemia

Ceruloplasmin is needed for release of iron from macrophages

Question 15

Where is iron located on liver biopsy:
HH->
Transfusional Iron Overload->

Answer 15

HH-> liver parenchyma

Transfusional-> Kupffer cells

Question 16

Patient presents with elevated ferritin and low transferrin saturation. Liver MRI shows iron overload. Biopsy shows distribution of iron in kupffer cells
Diagnosis:
Gene mutation

Answer 16

Ferroportin Disease

FPN1 gene mutation. Autosomal dominant

Question 17

Gene mutation seen in juvenile hemochromatosis

Answer 17

HJV. Lowers hepcidin and causes increased iron absorption from the gut

Question 18

What does hepcidin do?

Answer 18

inhibits mobilization of iron from tissue macrophages and absorption of iron from the GI tract by decreasing ferroportin levels