Porphyrias

Question 1

Acute intermittent porphyria

Answer 1

Autosomal dominant

HMB synthase deficiency

(Hydroxymethylbilane) synthase

Abdo pain, seizures, psych change, nausea, vomiting, sensory loss, muscle weakness, constipation, urinary incontinence

Neurovisceral symptoms ONLY
No porphyrinogens produced to cause cutaneous lesions

Can CAUSE SIADH –> Hyponatraemia

Diagnosis
Increased ALA (pre-cursor)
Increased PBG in urine (pre-cursor) = “port-wine urine”

Precipitating Factors
ALA synthase inducers (barbituates, steroids, ethanol)
Stress = infection or surgery
Reduced caloric intake
Endocrine (premenstrual) 

Tx
IV haem arginate
IV carbohydrate

Question 2

Non-Acute Porphyrias

Answer 2

Skin lesions ONLY

Congenital Erythropoietic Porphyria (CEP)

Erythropoietic Protoporphyria (EPP) = most common in children

Porphyria Cutanea Tarda (PCT)= most common

Question 3

Acute Porphyrias WITH skin lesions

Answer 3

Blistering skin condition AND Neurovisceral

Hereditary coproporphyria (HCP)

Variegate porphyria (VP)

Autosomal dominant

Raised prophyrins in faeces or urine

Question 4

porphyrins precursors cause…

Answer 4

Skin lesions

UV oxidised

Question 5

5-ALA causes…

Answer 5

Neurovisceral symptoms

Toxic

Question 6

Prophyrinogens

Answer 6

= no double bond in joining bridge

Question 7

Porphyrins

Answer 7

= double bond in joining bridge

Gives colour

Question 8

Most common in children

Answer 8

Erythropoietic Protoporphyria (EPP)

Question 9

Most common Porphyria

Answer 9

Porphyria Cutanea Tarda (PCT)

Question 10

X-linked sideroblastic anaemia

Answer 10

ALA Synthase deficiency

NOT a porphyria

Question 11

ALA Dehydratase Porphyria or Plumboporphyria

Answer 11

PBG Synthase deficiency

Increase ALA
But no PBG!

Neurovisceral symptoms
Abdo pain
Coma
Palsy 
Motorneuropathy

Question 12

Hereditary Coproporphyria (HCP)

Answer 12

Coproporphyrinogen oxidase deficiency

Autodomal dominant

Acute neurovisceral attack

Skin lesions
Blistering (back of hands and neck, sun exposed)
Skin fragility

Question 13

Variegate Porphyria (VP)

Answer 13

Protoporphyrinogen oxidase deficiency

Autosomal dominant

Acute attacks

Skin lesions: blistering cutaneous

Question 14

Why don’t all porphyrias have Neurovisceral Symptoms?

Answer 14

ALA responsible for neurovisceral symptoms

Protoporphyrinogen IX and Coproporphyrinogen III are potent inhibitors of HMB synthase –> backlog of PBG –> raised ALA –> neurovisceral symtpoms

In other prophyrias there is no inhibition of HMB, ALA will continually be mtebaolised

Question 15

Differentiating Acute Porphyrias

Answer 15

AIP – no skin lesions

HCP & VP – skin lesions

Urine PBG – raised in all three

Urine and faeces for porphyrins - Raised HCP or VP, but not AIP

Question 16

Porphyria Cutanea Tarda

Answer 16

Inherited or acquired

Uroporphyrinogen decarboxylase deficiency

Formation of vesicles on sun-exposed areas of skin crusting, superficial scarring, pigmentation

Biochemistry:

Urinary (& plasma) uroporphyrins & coproporphyrins increased
Ferritin often increased

Avoid precipitants (alcohol, hepatic compromise)

Question 17

Erythropoietic protoporphyria

Answer 17

Photosensitivity only, no blisters

Ferrochetalase deficiency

ONLY non-blistering porphyria

Most common in children

Only erythroid cells affected, therefore need to measure RBC protoporphyrin

Question 18

Non-blistering Porphyria

Answer 18

Erythropoietic protoporphyria

Question 19

Autosomal dominant

HMB synthase deficiency

(Hydroxymethylbilane) synthase

Abdo pain, seizures, psych change, nausea, vomiting, sensory loss, muscle weakness, constipation, urinary incontinence

Neurovisceral symptoms ONLY
No porphyrinogens produced to cause cutaneous lesions

Can CAUSE SIADH –> Hyponatraemia

Diagnosis
Increased ALA (pre-cursor)
Increased PBG in urine (pre-cursor) = “port-wine urine”

Precipitating Factors
ALA synthase inducers (barbituates, steroids, ethanol)
Stress = infection or surgery
Reduced caloric intake
Endocrine (premenstrual) 

Tx
IV haem arginate
IV carbohydrate

Answer 19

Acute intermittent porphyria

Question 20

Skin lesions ONLY

Congenital Erythropoietic Porphyria (CEP)

Erythropoietic Protoporphyria (EPP) = most common in children

Porphyria Cutanea Tarda (PCT)= most common

Answer 20

Non-Acute Porphyrias

Question 21

Blistering skin condition AND Neurovisceral

Hereditary coproporphyria (HCP)

Variegate porphyria (VP)

Autosomal dominant

Raised prophyrins in faeces or urine

Answer 21

Acute Porphyrias WITH skin lesions

Question 22

Skin lesions

UV oxidised

Answer 22

porphyrins precursors cause…

Question 23

Neurovisceral symptoms

Toxic

Answer 23

5-ALA causes…

Question 24

= no double bond in joining bridge

Answer 24

Prophyrinogens

Question 25

= double bond in joining bridge Gives colour

Answer 25

Porphyrins

Question 26

Erythropoietic Protoporphyria (EPP)

Answer 26

Most common in children

Question 27

Porphyria Cutanea Tarda (PCT)

Answer 27

Most common Porphyria

Question 28

ALA Synthase deficiency NOT a porphyria

Answer 28

X-linked sideroblastic anaemia

Question 29

PBG Synthase deficiency Increase ALA But no PBG! ``` Neurovisceral symptoms Abdo pain Coma Palsy Motorneuropathy ```

Answer 29

ALA Dehydratase Porphyria or Plumboporphyria

Question 30

Coproporphyrinogen oxidase deficiency Autodomal dominant Acute neurovisceral attack Skin lesions Blistering (back of hands and neck, sun exposed) Skin fragility

Answer 30

Hereditary Coproporphyria (HCP)

Question 31

Protoporphyrinogen oxidase deficiency Autosomal dominant Acute attacks Skin lesions: blistering cutaneous

Answer 31

Variegate Porphyria (VP)

Question 32

ALA responsible for neurovisceral symptoms Protoporphyrinogen IX and Coproporphyrinogen III are potent inhibitors of HMB synthase --> backlog of PBG --> raised ALA --> neurovisceral symtpoms In other prophyrias there is no inhibition of HMB, ALA will continually be mtebaolised

Answer 32

Why don't all porphyrias have Neurovisceral Symptoms?

Question 33

AIP – no skin lesions HCP & VP – skin lesions Urine PBG – raised in all three Urine and faeces for porphyrins - Raised HCP or VP, but not AIP

Answer 33

Differentiating Acute Porphyrias

Question 34

Inherited or acquired Uroporphyrinogen decarboxylase deficiency Formation of vesicles on sun-exposed areas of skin crusting, superficial scarring, pigmentation Biochemistry: Urinary (& plasma) uroporphyrins & coproporphyrins increased Ferritin often increased Avoid precipitants (alcohol, hepatic compromise)

Answer 34

Porphyria Cutanea Tarda

Question 35

Photosensitivity only, no blisters Ferrochetalase deficiency ONLY non-blistering porphyria Most common in children Only erythroid cells affected, therefore need to measure RBC protoporphyrin

Answer 35

Erythropoietic protoporphyria

Question 36

Erythropoietic protoporphyria

Answer 36

Non-blistering Porphyria