Heme synthesis and pathology

Question 1

Mnemonic for hemoglobin development sites

Answer 1

“young Liver Synthesizes Blood”

Yolk sac (week 3-8)
Liver (week 6- birth)
Spleen (Week 10 -28 weeks)
Bone marrow (Week 18- adult; prominent week 28)

Question 2

Composition of embryonic fetal globins

Answer 2

Hb Gower – 2 zeta 2 epsilon

Question 3

Fetal hemoglobin?

Answer 3

Hb F:

2 alpha 2 delta

Question 4

Adult hemoglobin

Answer 4

Hb A:

2 alpha 2 beta

Question 5

2% of normal hemoglobin is composed of?

Answer 5

Hb A 2 :

2 alpha, 2 delta

Question 6

Hb in poorly controlled diabetes:

Answer 6

Hb A1c:

2 alpha 2 beta–glucose

Question 7

Sickle cell hemoglobin

Answer 7

HbS :

2 alpha 2 beta S ( glu–> val in beta chain)

Question 8

Hemoglobin C disease

Answer 8

Also seen in sickle cell population

HbC:

2 alpha 2 beta (glu –> lysine in beta chain)

Question 9

Type of hemoglobin you see in severe alpha thalassemia

• 3 mutations?
• 4 mutations?

Answer 9

Hb H: ( 3 mutations)
4 beta ( no alpha chains)

Hb Bart’s: (4 mutations)
4 gamma ( no alpha chains)
- hydrops fetalis and death

Question 10

Lead poisoning:

Enzyme blocked?

Accumulated substrate?

Presenting symptoms?

tx?

Answer 10

Aminolevulinic acid (ALA) dehydratase
Ferrochelatase

Delta-aminolevulinic acid ( delta- ALA) and
Protoporphyrin

• Microcytic anemia
• Encephalopathy
• Memory loss + delirium + mental deterioration
• Foot drop/ wrist drop
• Microcytic anemia and basophilic stippling + siderblastic anemia (in bone marrow)
• Lead lines in gums and bones (children)
• colicy abdominal pain
• renal failure in adults

EDTA or Succimer for adults and children

If very severe toxicity = Dimercaprol + succimer

Question 11

Acute intermittent prophyria

Enzyme blocked?

Accumulated substrate?

Presenting symptoms?

tx?

Answer 11

Porphobilinogen deaminase ( aka uroporphinogen-1-synthase deficiency)

Porphobilinogen, delta ALA, coporphobilinogen (urine)

5 P’s:

Painful abdomen
Port wine colored urine
Polyneuropathy
Psychological disturbances
Precipitaed by drugs (barbituates, seizure drugs, rifampin, and methoclopramide; cytochrome P-450 inducers, alcohol, and starvation

Tx: glucose and heme – inhibit ALA synthase

Question 12

Porphyria cutanea tarda

Enzyme blocked?

Accumulated substrate?

Presenting symptoms?

Answer 12

Uroporphyrinogen decarboxylase

Uroporphyrin ( tea colored urine)

Symptoms:

• blistering of skin and photosensitivity
• tea colored urine
• Hypertrichosis (facial hair growth)
• Facial hyperpigmentation
• Hep C
• Alcoholism

Question 13

Hemoglobin in beta- thalassemia

Answer 13

(2 genes)

Beta - thalassemia minor

• beta chain is underproduced
• asymptomatic
• diganosis confirmed with an increasei n HbA 2

Beta thalassemia major
- Beta chain is absent –> severe anemia