Acute Intermittent Porphyria

Question 1

Porphyrias a rare hereditary disease in which there is abnormal metabolism of the blood pigment haemoglobin. What is the incidence of this disease?

1 - 1/100,000
2 - 1/10,000
3 - 1/1000
4 - 1/100

Answer 1

3 - 1/1000

Question 2

What type of genetic inheritance is Porphyrias?

1 - autosomal dominant
2 - X linked dominant
3 - autosomal recessive
4 - X-linked recessive

Answer 2

3 - autosomal recessive

Question 3

Haemoglobin is the main protein in RBCs that carries O2. Which 2 components make up haemoglobin?

1 - bilirubin
2 - heme
3 - globin
4 - glucose

Answer 3

2 - heme
3 - globin

Question 4

How many different globins are present on each haemoglobin?

1 - 1
2 - 2
3 - 4
4 - 8

Answer 4

2 - 2
- each haemoglobin has 2 alpha and 2 beta globin
- each globin has one haem group

Question 5

Each haemoglobin is composed of 2 alpha and 2 beta globulins, each with their own haem group. How many heam groups are present on each globin?

1 - 8
2 - 6
3 - 4
4 - 1

Answer 5

4 - 1

Question 6

There is one haem to every globin, means each haemoglobin has:

• 4 globin (2 alpha and 2 beta)
• 4 haem groups

Haem is composed of 4 pyrrole subunits forming a ring, and this structure is called a porphyrin. What molecule can be found in the middle of the haem?

1 - Fe2+
2 - Mg2+
3 - Na+
4 - Ca2+

Answer 6

1 - Fe2+
- this is what binds and carries O2 around the body

Question 7

How many O2 molecules can each haemoglobin molecule carry?

1 - 16
2 - 8
3 - 4
4 - 1

Answer 7

3 - 4
- carries 1 in each haem

Question 8

In a cell, which 2 places does the synthesis of haem begin?

1 - nucleus
2 - mitochondria
3 - cytosol
4 - rough endoplasmic reticulum

Answer 8

2 - mitochondria
3 - cytosol

• requires lots of enzymes

Question 9

Haem synthesis begins in the mitochondria and the cytosol. In the cytosol which important enzyme is responsible for converting 4 molecules of porphobilinogen into hydroxymethylbilane?

1 - succinyl-CoA
2 - delta-ALA dehydratase
3 - porphobilinogen deaminase
4 - hydroxymethylbilane synthase

Answer 9

3 - porphobilinogen deaminase
- mutations is this is what we need to know about
- leads to reduces haem and increased metabolites from earlier stages in haem synthesis

Question 10

In a rare autosomal recessive disease where the porphobilinogen deaminase is mutated, leads to a build up to metabolites that can become toxic to the body. Which of the following are the 2 toxic substances that build up?

1 - lactic acid
2 - porphobilinogen
3 - hydrogen peroxidase
4 - aminolevulinic acid

Answer 10

2 - porphobilinogen
4 - aminolevulinic acid
- both are toxic to the body

Question 11

Do all patients with acute intermittent porphyria present with symptoms?

Answer 11

• no

Question 12

Not all patients with acute intermittent porphyria present with symptoms. Do men or women present more with symptoms?

Answer 12

• women
• 10% young women present with symptoms, specifically if triggered, where haem production needs to be increased

Question 13

Which of the following ate triggers that may cause symptoms in a patient with acute intermittent porphyria?

1 - excessive alcohol
2 - stavation
3 - medications that upregulate CYP450
4 - all of the above

Answer 13

4 - all of the above

• CYP450 contains haem and is required in the liver to metabolise drugs

Question 14

The 2 metabolites that can build up in patients with acute intermittent porphyia are:

• porphobilinogen
• aminolevulinic acid

Of these 2 which is able to cross the BBB?

Answer 14

• aminolevulinic acid
• can affect autonomic, CNS and PNS function

Question 15

Which of the following is NOT a CNS symptoms that can present in acute intermittent porphyia?

1 - delirium
2 - GIT dysmotility
3 - coma
4 - anxiety/psychosis
5 - seizures

Answer 15

2 - GIT dysmotility
- autonomic symptom

Question 16

Which of the following is NOT an autonomic symptoms that can present in acute intermittent porphyia?

1 - GIT dysmotility
2 - constipation
3 - abdominal pain
4 - vomiting
5 - diarrhoea

Answer 16

5 - diarrhoea
- in the GIT patients present with what appears to be GIT obstruction

Question 17

Which of the following is NOT an PNS symptoms that can present in acute intermittent porphyia?

1 - peripheral neuropathy
2 - paresthesia
3 - DVT

Answer 17

3 - DVT

Question 18

When trying to remember the key symptoms of acute intermittent porphyia, there are 4Ps. Which of the following is NOT one of these in acute intermittent porphyria?

1 - Pain in the abdomen
2 - Port coloured urine
3 - Polyneuropathy
4 - Photosensitivity
5 - Psychological disturbance

Answer 18

4 - Photosensitivity
- All other porphyria have this and it causes skin blistering

• port coloured wine = only changes colour when the urine is exposed to light
• porphobilinogen in urine undergoes oxidation and becomes wine colour

Question 19

Which 2 of the following can be used to diagnose a patient with suspected acute intermitten porphyria?

1 - bone marrow biopsy
2 - urinalysis for porphobilinogen
3 - lab analysis of erythrocyte porphobilinogen deaminase activity
4 - RBC with MVC

Answer 19

2 - urinalysis for porphobilinogen

3 - lab analysis of erythrocyte porphobilinogen deaminase activity

• patients may also present with hyponatraemia and elevated liver enzymes due to excessive metabolites produced

Question 20

Which of the following are treatment for patients with acute intermittent porphyria?

1 - Intravenous dextrose
2 - Haem arginate
3 - Managing pain and electrolyte abnormalities
4 - RNA interference ATMP gene therapy Givosiran (ALN-AS1)
5 - all of the above

Answer 20

5 - all of the above