Porphyrias Flashcards
What are porphyrias?
They are diseases caused by a deficiency of enzymes involved in haem biosynthesis, causing a higher concentration of toxic precursors.
Describe the haem synthesis pathway. How does the water solubility of the compounds change as you go down the chain?
Succinyl CoA and Glycine
- ALA Synthase
ALA
- PBG Synthase
PBG
- HMB Synthase
HMB
- Uro III Synthase
Uroporphyrinogen III (Uroporphyrinogen I if no enzyme) - Uro Decarboxylase
Coproporphyrinogen
- Copro oxidase
Protoporphyrinogen IX
- Proto oxidase
Protoporphyrin IX
- Ferrochetalase
Haem
The compounds become less water soluble as you go down the chain.
What is the best way to classify porphyrias?
- Acute porphyrias with no cutaneous symptoms
- Acute porphyrias with cutaneous symptoms
- Non-acute porphyrias with cutaneous symptoms
- Non-acute porphyrias with no cutaneous symptoms
Name the different types of porphyrias
Acute porphyrias with no cutaneous symptoms
- Acute Intermittent Porphyrias
- Plumboporphyria
Acute porphyrias with cutaneous symptoms
- Hereditary coproporphyria
- Variegate porphyria
Non-acute porphyrias with cutaneous symptoms
- Congenital erythropoietic porphyria
- Porphyria cutanea tarda
Non-acute porphyrias with no cutaneous symptoms
- Erythropoietic protoporphyria
What is the most common porphyria?
Porphyria cutanea tarda
What is the most common porphyria in children?
Erythropoietic protoporphyria
How does Acute Intermittent Porphyria present? What is the biochemistry involved? What is the inheritance?
It usually follows a precipitating factor (alcohol, stress, steroids, reduced caloric intake)
It is a constellation of neurovisceral symptoms (abdo pain, seizures, psych disturbances, N&V, sensory loss, tachycardia) with NO cutaneous symptoms
Biochemistry:
It is a deficiency in HMB synthase, causing an increase in ALA and PBG.
It is an autosomal dominant inheritance
How should any acute porphyria be investigated?
Sending off a urine PBG, keeping it away from light.
How does hereditary coproporphyria and variegate porphyria present? What is the biochemistry involved? What is the inheritance?
These are acute porphyrias with cutaneous symptoms
You will have a constellation of neuro-visceral symptoms (abdo pain, psych disturbances, N&V, seizures) WITH cutaneous symptoms (blistering lesions and fragile skin in sun exposed areas)
Biochemistry:
HCP is a deficiency in copro oxidase, causing an increase in the concentration of copro
VP is a deficiency in proto oxidase, causing an increase in the concentration of proto
Both copro and proto cause HMB synthase inhibition, raising the concentrations of PBG and ALA
They are both an autosomal dominant pattern of inheritance
How should HCP and VP be investigated?
With a stool sample. The toxic precursors involved are less water soluble, so will be found in the stool.
Why does AIP present with hyponatraemia?
This is as a result of SIADH
Are most cases of those with a HMB synthase deficiency symptomatic?
No, 90% are asymptomatic, as 50% of the enzyme is functioning. It only becomes symptomatic in precipitating factors.
How should AIP be managed?
Immediately prescribe haem arginase, to inhibit the activity of ALA synthase.
Then, advise to avoid any precipitating factors and inducers of cytochrome P450.
How can you differentiate between the acute porphyrias?
First, take a urine PBG to confirm it is a porphyria.
Then, send for urine/faecal porphyrins to look at proportions:
- Raised in HCP and VP
- Not raised in AIP
Enzyme activity to determine which enzyme is deficient (note: can be variable).
How is EPP different to CEP and PCT?
Erythropoietic porphyria does not present with blistering cutaneous lesions, whereas congenital erythropoietic porphyria and porphyria cutanea tarda do.
