Lecture 8 (Part 1) Porphyrias

Question 1

where does haem synthesis occur?

Answer 1

Haem synthesis occurs in the cytosol and mitochondria;

Question 2

What stimulates Globin chain synthesis, RBC formation and haem synthesis

Answer 2

In immature erythrocytes (reticulocytes), haem stimulates protein synthesis of the globin chains and erythropoietin stimulates haem

The kidney releases erythropoietin hormone at low oxygen levels in tissues and stimulates RBC and haemoglobin synthesis.

Question 3

What stops haem synthesis

Answer 3

haem synthesis stops when haem is not incorporated into proteins and when haem and hemin accumulate.

Question 4

Define Porphyria

Answer 4

The porphyrias are a group of seven rare diseases characterized by chronic skin manifestations (cutaneous porphyrias) or by intermittent acute attacks of illness (acute porphyrias).

A group of disorders caused by deficiencies of enzymes involved in the production of haem.

Question 5

Classify acute vs cutaneous porphyria

Answer 5

Acute porphyrias: Porphyrias that cause neurologic, mental, and abdominal symptoms

Cutaneous porphyrias: Porphyrias that cause skin symptoms when the skin is exposed to sunlight

Question 6

Other Classification methods

Answer 6

Based on where excess precursors orginate

Hepatic porphyrias: Precursors originate primarily in the liver

Erythropoietic porphyrias: Precursors originate primarily in the bone marrow

Question 7

Diagram of haem synthesis with all enzymes and porphyria types

Answer 7

Lecture Slide

Question 8

Examples of acute porphyria

Answer 8

Acute intermittent 
Variegate porphyria (VP)
Hereditary coproporphyria (HP)

Question 9

Cutaneous porphyrias examples

Answer 9

When exposed to light and oxygen, these porphyrins generate an unstable form of oxygen capable of damaging the skin

1. Porphyria cutanea tarda (PCT), the most common
   cutaneous porphyria
2. Congenital erythropoietic porphyria (CEP)
3. Hepatoerythropoietic porphyria (HEP)

Question 10

Which porphyria is auto dominant

Answer 10

Acute intermittent
hereditary coproporphyria
variegate porphyria.

Question 11

Which porphyria is auto recessive

Answer 11

1. ALAD deficiency porphyria,
2. congenital erythropoietic porphyria
3. Hepatoerythropoietic porphyria
4. erythropoietic protoporphyria.

Question 12

Which porphyria is auto dom/recessive/acquired

Answer 12

Cutaneous Tarda

Question 13

Inital screening based on..

Answer 13

Measuring porphyrins and porphyrin precursors in the
urine, faeces or blood

symptoms:
Acute attacks of severe abdominal pain, nausea, vomiting, rapid heartbeat and other symptoms.

test:
Spot urine porphobilinogen (PBG) and total porphyrins*

symptoms:
Blistering skin photosensitivity (with or without acute attack symptoms)

Test:
plasma or urine total porphyrins

Question 14

Secondary Testing

Answer 14

1. Stool Porphyrins
   Once a diagnosis of acute porphyria has been made, used to differentiate HCP, VP and AIP

Total Plasma Porphyrins
differentiate VP from other porphyria

Erythrocyte Porphyrins
differentiate PCT from HEP and CEP

Question 15

4 reasons why Acute Porphyrias are missed or misdiagnosed

Answer 15

Nonspecific symptoms: symptoms of an acute attack can be caused by many other things

Variable symptoms: no single symptom or constellation of symptoms is universal in all patients

Missing or incomplete Family History: about 1/3 of the time, there is no family history of the disease because the disease has been latent for several generations

Wrong tests are ordered and/or test results are not available promptly because they cannot be done on site

Question 16

Why is an accurate diagnosis of Porphyria so important?

Answer 16

Prompt diagnosis is important because delays can result in irreversible neurologic damage

Many of the medications used to treat the nonspecific symptoms of porphyria are drugs that can precipitate or worsen acute attacks

Untreated attacks can result in long-term or permanent
paralysis, coma, neurological damage, or even death

Question 17

Correct Collection of Specimens

Answer 17

u Use light-proof bottle (wrap it in aluminum foil.)

Urine should be alkalinized and refrigerated.

Question 18

First line of testing:

Answer 18

1.Porphobilinogen
recommended when AIP, HCP, or VP is suspected

2.Urine Porphyrin Fractionation and Quantitation
used to evaluate patients for porphyrias that manifest with blistering cutaneous photosensitivity.

3.Erythrocyte Porphyrin (red cell)
first-line test for evaluating patients for suspected protoporphyrias (EPP )