Heme Synthesis, Degradation and Porphyrias - Part 2

Question 1

What are erythropoietic porphyrias?

Answer 1

Erythroid Porphyria means that an enzyme of heme synthesis in erythroid cells of the bone marrow is deficient. This leads to microcytic anemia and can also lead to damage of skin and other organs

Question 2

What are two examples of erythropoietic porphyrias?

Answer 2

• Congenital Erythropoietic Porphyria

- Erythropoietic Protoporphyria

Question 3

What are two examples of hepatic porphyrias?

Answer 3

• Acute Intermittent Porphyria (AIP)

- Porphyria Cutanea Tarda (PCT)

Question 4

Describe Congenital Erythropoietic Porphyria.

Answer 4

Congenital Erythropoietic Porphyria leads to severe and extremely painful photosensitivity and possible “werewolf” appearance of patients and mental disturbance

Question 5

Which age group would you expect for a patient with Congenital Erythropoietic Porphyria, Acute Intermittent Porphyria or Porphyria Cutanea Tarda, respectively?

Answer 5

• CEP: early childhood
• AIP: 40-50 yr/old adults
• PCT: adults & can be hereditary aquired

Question 6

Is Porphyria Cutanea Tarda (PCT) an acute or a chronic disease? What triggers it? Is it rare?

Answer 6

• Chronic disease found in the liver.
• It can be triggered by factors like hepatic iron overload, exposure to sun light, ethanol abuse, hepatitis or HIV infections
• Most common porphyria

Question 7

A patient with severe abdominal pain, highly agitated state and respiratory problems, and no photosensitivity most likely has which porphyria?

Answer 7

-Acute Intermittent Porphyria
with high ALA and porphobilinogen
levels in blood that can act like neurotransmitters.
-No photosensitivity as the deficiency of HMB synthase does not allow formation of HMB.

Question 8

A patient with severe photosensitivity, reddish brown teeth, ulcers in the face, and onset early childhood most likely has which porphyria?

Answer 8

Congenital Erythropoietic Porphyria
with severe photosensitivity due to accumulation of red-colored uroporphyrin I and coproporphyrin I in blood and tissues. Severe damage due to radical formation in the skin.

Question 9

A patient with photosensitivity, skin eruptions, adult onset, most likely has the most common porphyria, which is what?

Answer 9

Porphyria Cutanea Tarda

with photosensitivity due to accumulation of red uroporphyrin III in blood and tissues. Hereditary and acquired

Question 10

Describe the urine color of patients with AIP and why.

Answer 10

urine has normal color upon release but then starts to darken.
-High levels of porphobilinogen lead from Colorless porphobilinogen to purple porphobilin in urine after contact with light and oxygen

Question 11

Describe the urine color of patients with PCT and why

Answer 11

Urine is already red upon release due to spontaneous formation of uroporphyrin III from the colorless uroporphyrinogen III inside the body

Question 12

Describe the urine color of patients with CEP and why.

Answer 12

urine has a similar red color like in PCT patients. The red color is due to uroporphyrin I and coproporphyrin I

Question 13

Which porphyrias cause patients to have red colored urine upon release?

Answer 13

PCT

CEP

Question 14

Prophobilinogen deaminase is needed for synthesis of what?

Answer 14

HMB (hydroxymethylbilane) synthesis

Question 15

What is the first molecule in heme synthesis that can be closed in a porphyrin ring system?

Answer 15

HMB (hydroxymethylbilane)

formed by: Porphobilinogen deaminase

Question 16

After what step in heme synthesis, if defective, can lead to photosensitivity?

Answer 16

• If the deficient enzyme catalyzes a step before synthesis of HMB, or directly the formation of HMB, then the patients are not photosensitive.
• Enzyme deficiencies of heme synthesis after formation of HMB lead to photosensitivity due to accumulation of “faulty” porphyrin rings. These abnormal free porphyrins in the blood can lead in the skin to extensive radical formation due to sunlight and to painful skin damage

Question 17

Acute Interpittent Porphyria:

• Enzyme deficient?
• What accumulates?

Answer 17

• HMB Synthase (porphobilinogen deaminase)

- ALA and porphobilinogen in blood and urine

Question 18

Congenital Erthyroid Porphyria:

• Enzyme deficient?
• What accumulates?

Answer 18

• Uroporphyrinogen III synthase

- Red urophorphyrin I and Red Coproporphyrin I in blood, tissues and urine

Question 19

Porphyria Cutanea Tarda:

• Enzyme deficient?
• What accumulates?

Answer 19

• Uroporphyrinogen Decarboxylase

- red uroporphyrin III in blood, tissue and urine

Question 20

Name conditions that lead to microcytic anemia.

Answer 20

• In general: deficiency of heme and hemoglobin leads to microcytic anemia.
• Deficiency of intracellular iron in erythroid cells leads to reduced activity of ALAS2
• Deficiency of vitamin B6 (PLP) leads to reduced activity of ALAS2
• Lead poisoning leads to microcytic anemia as it inhibits ALA dehydratase and ferrochelatase. Lead binds to sulfhydryl groups and also interferes with the zinc cofactor needed for both enzymes
• deficiency of copper leads indirectly to microcytic anemia. Copper is needed for ceruloplasmin which forms the ferric iron which is transported by transferrin in the blood and stored inside of cells in ferritin