Extra Material on Porphyrias

Question 1

What forms the basis of all porphyrias?

Answer 1

Cells fails to change porphyrin and porphyrin precursors into haem

Question 2

What is the difference between acute and cutaneous porphyrias?

Answer 2

Acute = largely affects nervous system
Cutaneous = largely affects skin

Question 3

What is the difference between erythropoietic and hepatic porphyrias?

Answer 3

Erythropoietic = bone marrow over produces porphyrin
Hepatic = liver over produces porphyrin and it’s precursors

Question 4

What enzyme is deficient in acute intermittent porphyria?

Answer 4

Porphobilinogen deaminase = causes porphyrin build up in liver

Question 5

What enzyme is deficient in porphyria cutanea tarda?

Answer 5

Uroporphyrinogen decarboxylase = causes porphyrin build up in liver

Question 6

What enzyme is deficient in erythropoietic protoporphyria?

Answer 6

Ferrochelatase = causes porphyrin build up in bone marrow

Question 7

What is needed to cause symptoms in acute intermittent porphyrias?

Answer 7

Activating factor = after puberty, steroids, barbiturates, smoking, stress

Question 8

What is the main symptom of acute intermittent porphyria?

Answer 8

Abdominal pain = may be severe or associated with nausea

Question 9

What are some other symptoms of acute intermittent porphyrias?

Answer 9

Muscle weakness in limbs, agitation, insomnia, urinary retention

Question 10

What are patients with acute intermittent porphyria at a higher risk of developing?

Answer 10

Hepatocellular carcinomas and kidney failure

Question 11

What mutation causes acute intermittent porphyria?

Answer 11

Mutation in HMBS gene = inheritance is autosomal dominant

Question 12

How is acute intermittent porphyria diagnosed?

Answer 12

Elevated urine ALA and porphobilinogen (PBG), PBGD deficiency in normal red blood cells

Question 13

What is the main symptom of porphyria cutanea tarda?

Answer 13

Photosensitivity = painful blistering of sun exposed skin, skin fragility (May peel or blister on minor trauma)

Question 14

How else may skin be affected on porphyria cutanea tarda?

Answer 14

Increased hair growth, thickening and darkening of skin

Question 15

What other organ is affected by porphyria cutanea tarda?

Answer 15

Liver = increased risk of liver cirrhosis and carcinoma

Question 16

What are some risk factors for developing porphyria cutanea tarda?

Answer 16

Excess iron, alcohol, smoking, oestrogen, chronic hepatitis C, HIV, mutations in HEF gene

Question 17

What is a rare cause of porphyria cutanea tarda?

Answer 17

Familial inheritance = mutations in UROD gene, autosomal dominant

Question 18

How may porphyria cutanea tarda be treated?

Answer 18

Regular phlebotomies

Question 19

What mutation causes erythropoietic protoporphyrias?

Answer 19

Mutation in FECH gene = autosomal recessive inheritance

Question 20

Where can FECH build up in erythropoietic porphyrias?

Answer 20

Bone marrow, red blood cells, blood plasma, skin and eventually liver

Question 21

What can erythropoietic porphyria lead to?

Answer 21

Extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, splenomegaly

Question 22

What are the common symptoms of erythropoietic porphyria?

Answer 22

Skin photosensitivity, erythema, pruritis

Question 23

How is erythropoietic porphyria treated?

Answer 23

Sun avoidance and avoidance of UV exposure, vitamin D supplements, protective clothing, liver complications may need transplant