Porphyrias

Question 1

How are the majority of Porphyrias inherited?

Answer 1

Autosomal dominant fashion

Question 2

What is a key indicator of a porphyria?

Answer 2

Having differently coloured skin, urine, teeth which are a result of the toxic byproducts of build up of heme synthesis precursors

Question 3

Why can we not have a Porphyria of the ALAS enzyme in the pathway?

Answer 3

This would be incompatible with life

Question 4

What enzymes in the synthesis pathway are considered to be early lesion enzymes?

Answer 4

ala dehydratase and porphobilinogen deaminase

Question 5

what does a lesion in ala dehydratase lead to accumulation of?

Answer 5

ALA

Question 6

what does a lesion in porphobilinogen deaminase lead t o an accumulation of?

Answer 6

Porphobilinogen

Question 7

what are the build up products of the early lesion enzymes toxic too?

Answer 7

they are neurotoxic specifically to the nerves in the abdomen

Question 8

what are the symptoms of a early lesion porphyria attack?

Answer 8

severe abdominal pain, hallucinations, vomiting, constipation, diarrhoea.

Question 9

What is there a decreased level of in early lesion prophyrias

Answer 9

Reduced heme in body cells and body fluids

Question 10

What is an example of a porphyria that is considered to be an early lesion porphyria?

Answer 10

Acute intermittent Porphyria.

Question 11

Why is the oral contraceptive risk for those who have AIP?

Answer 11

in a study this triggered an attack in 24% of women who took the pill

Question 12

What two things are measured to diagnose AIP?

Answer 12

you would do a PBGD assay from PBGD taken from erythrocyte cells to diagnose type 1 and 3 AIP
you can also measure urinary levels of PBG and ALA.

Question 13

What is the prevalence of AIP

Answer 13

1 in 10,000 people in the UK have this gene defect but only 1 in many thousands actually go on to have an attack

Question 14

What do later legions in the heme synthesis pathway produce?

Answer 14

build up of metabolically useless Porphyrins

Question 15

what enzyme is affected in congenital erythropoietic porphyria?

Answer 15

uroporphyrinogen 3 co synthase

Question 16

what classes of porphyringoen are produced in later lesion porphyrias?

Answer 16

class one instread of class 3

Question 17

what are the class 3 porphyrinogens made into?

Answer 17

they are autooxidised to make metabolically useless and toxic porphyrins

Question 18

what are the main symptoms of congential erythropoietic porphyria?

Answer 18

red pee
fluorescent teeth
Photosensitivity
anaemia

Question 19

how many recognised porphyrias are there?

Answer 19

8

Question 20

What is the most common kind of porphyria?

Answer 20

Porphyria cutanea tarda

Question 21

what enzyme is affected in pct and whaht does this cause the build up of?

Answer 21

uroporphyrinogen decarboxylase which leads to build up of uroporphyrinogen 3 which then gets oxidised to useless type 1 Porphyrins.

Question 22

how would you diagnose this?

Answer 22

red wine coloured pee with excess uroporphyrin 1 in urine

also you can look for elevated uroporphyrins in the faeces and in the plasma.

Question 23

what is the first type of porphyria cutanea tarda characterised by?

Answer 23

its not genetics,but there is decreased activity of hepatic uroporphyrinogen decarboxylase

Question 24

what is the the second type of porphyria cutanea tarda caused by?

Answer 24

by an autosomal dominant mutation that results in overall decreased acitvity of uroporphyrinogen activity in all cells.

Question 25

what is the mean feature of type 3 porphyria cutanea tarda?

Answer 25

no genetic defect in actual gene but cannot be put with class one because often more than one person in the family has this suggesting some kind of genetic link

Question 26

what is the homozygous form of this porphyria cutanea tarda called?

Answer 26

hepatoerythropoietic porphyria

Question 27

what does a mutation in the HFE gene do

Answer 27

this is a gene that helps with the regulation of iron absorbtion, defects lead to an Fe overload which then induces a porphyria attack of the cutanea tarda kind

Question 28

what hormone can increase risk of a pct attack?

Answer 28

oestrogen

Question 29

how do the type 1 uroporphyrins cause skin blistering?

Answer 29

degranulation of the dermal mast cells which leads to the release of damaging proteases

Question 30

what colour are the type 1 uroporphyrins?

Answer 30

deep purple (Seen in skin)

Question 31

what can alcohol increase the activity of?

Answer 31

ALA synthase

Question 32

what deficiency can be caused to treat porphyria ct?

Answer 32

causing a slight Fe deficiency as this limits heme synthesis