Porphyrias Flashcards
What is a porphyria?
Group of diseases due to deficiencies in haem synthesis pathway
–> overporudction of toxic intermediate products
Recall the normal Haem synthesis pathway
Starts in the Mitochrondria –> move into cytoplasm –> end step in mitochrondria again
Where is haem mainly synthesised?
Majority is synthesised in the Liver + Bone Marrow
What are the main groups of signs and symptomas seen in porphyrias and what product is causing them?
- Neuroviscular symptoms: 5 ALA –> disorders early in the pathway (+ late, when deficiency of certain enzymes that normally have negative feedback on early enzymes)
- Blistering cutaneous
- Non-blistering cutaneous
What are the classic characteristics of a urine sample given by a patient with porphyria?
Colourless when given, then turns dark red, brown, purple by the time is reaches lab (due to oxidisation of compounds accumulating in urine)
What is the most common porphyria?
What is the epidemiology?
Porphyria cutanea tarda - 1 in 25.000
What is the most important acute porphyria?
Acute intermittent porphyria –> people can be very sick and present to A&E
What is the porphyria most commonly presenting in children?
Erythropoetic protoporphyria
3rd most common overall, higher prevalence in china + japan
What are the acute porphyrias?
What do they have in common, and how can you differentiate between them?
- Acute intermittent porphyria - no skin symptoms (only neurovisceral)
- HCP + VP: Neurovisceral AND skin symptoms (blistering) (Hereditary coproporphyria, Variegate porphyria)
Differentiate
Urine PBG – raised in all three
Urine and faeces for porphyrins
Raised HCP or VP, but not AIP
Enzyme activity variable
Explain the pathophysiologc of Acute intermittent Porphyria
Autosomal dominant disorder with incomplete penetrance (80-90% are asymptomatic)
It is an deficiency in HMB synthase (or reduced efficiency) –> increase in Prophobiliniogen and 5- ALA
–> neurolvisceral symptoms
What are the precipitating factors for an acute attack of Acute intermittent Porphyria?
ALA synthase inducers
- Barbiturates, steroids, ethanol, anticonvulsants
Stress - Infection, surgery
- Reduced caloric intake
- Endocrine factors
- More common in women and premenstrual
What are the symptoms of an acute attack of Acute intermittent porphyria?
5 P’s of acute intermittent porphyria: Painful abdomen, Polyneuropathy, Psychologic disturbances, Port wine-colored pee,Precipitated by triggers like drugs
Neurovisceral attacks
- Abdo pain and vomiting
- Tachycardia and hypertension
- Constipation, urinary incontinence
- Hyponatraemia +/- seizures
- Psychological symptoms
- Sensory loss / muscle weakness
- Arrythmias / cardiac arrest
No skin symptoms: No production of porphyrinogens –> too early in the pathway
How is Acute intermittent porphyria diagnosed?
Same as all acute porphyrias
Hard to do tests initially –> best test:
* Increased urinary PBG (and ALA)
PBG gets oxidised to porphobilin
Decreased HMBS activity in erythrocytes
How is acute intermittent Porphyria managed?
1. In an acute attack
2. chronic prevention
Usually by giving ALA synhthased inhibitors
- IV carbohydrates
- IV haem arginate
Prevention
1. avoid precipitating factors (drugs)
2. ensure adequate nutrition
What porphyrias have both, acute neurovisceral and blistering cutaeneous synmptoms?
Why?
- Hereditary coproporphyria
- Variegate porphyria
Both are deficienct in enzymes late in the pathway -.-> accumulation of Coprocophyrinogen –> skin symptoms
Loss of negative inhibition on HMB synthase (usually exipited by these deficient enuzymes) –> accumulation of ALA –> neurovisceral symptoms
What are the important non-acute porphyrias?
What do they have in common?
All cause skin symptoms
Usually later in the pathway
- Blistering: porphyria cutanea tarda (+Congenital erythropoietic porphyria)
- Non-blistering: Erythropoietic protoporphyria
What is the pathophysiology and aetiology of Porphyria cutaenea tarda?
Reduced activity in enzyme uroporphyrinogen III decarboxylase (UROD) → uroporphyrin accumulates in the skin → sunlight-dependent skin damage (chronic photosensitivity)
Generally often seen secondary to liver damage
* iron overload
* Hep B, C
* HIV etc.
What is the clinical presentation of Porphyria cuttanea tarda?
- Photosensitivity
- facial hyperpigmentation
- hypertrichosis
- blistering,
- milia, scarring
- exacerbated by ETOH
What is Erythropoietic protoporphyria?
What is the typical clinicla presenations?
In CHILDREN:
Non-blistering, redness on sun-exposed areas (minutes after exposure)
How should Erythropoietic protoporphyria
be investigated?
Needs to be done via **Red cell protoporphyrins ** as is so late in the pathway
Recall the investigations sent for the different types of porphyrias
