1. Porphyria
Dr S Spijkerman

2. Porphyria
A heterogenic group of inborn errors in the haem biosynthesis pathway.
An enzyme deficiency at any point in the pathway can cause accumulation of haem precursors.
These precursors cause the neuropathy which is responsible for the symptoms of the acute attacks of the disease. Different enzyme defects cause the different kinds of porphyria

3. Haem at the end of pathway → negative feedback to the rate-limiting enzyme in the pathway, called ALA synthase.
This prevents the formation of excessive precursors
Some events may trigger an acute attack in a genetically enzyme deficient (porphyric) patient in one of the following ways:
Induction of ALA synthase activity → ↑ formation of precursors → accumulation due to genetically deficient enzyme (can’t cope with ↑ load).
Increase in haem demand, thus decreasing the haem pool and reducing the negative feedback on ALA synthase.

4. Haem pathway

5. Triggers Table 1. Triggers of acute porphyric attacks Stress Infection
Alcohol
Starvation
Dehydration
Menstruation
Drugs – see table 2

6. Table 2: Drugs Indication UWC UWEC Avoid Anaesthesia Thiopentone
Etomidate
Analgesics
Tramadol
Mefenamic acid
Diclofenac
Ketorolac
Pentazocine
Tilidine
Sedatives/
anticonvulsives
Diazepam
Phenobarbitone
Antibiotics
Clindamycin
Metronidazole
Sulphonamides
Erythromycin
Co-trimoxazole
Chloramphenicol
Local anaesthetics -
Asthma
Aminophylline
Antiemetics
Metoclopramide

7. Clinical presentation
Chronic types cause skin reactions (bullae, rash etc) → not life threatening

8. Clinical presentation – acute attack
Possible symptoms of an acute porphyric attack
(remember: accumulation of precursors cause neuropathy)
Sensory neuropathy
Motor neuropathy: Respiratory muscles, quadriparesis
Autonomic neuropathy: Abdominal pain, nausea and vomiting (causing dehydration), tachycardia, hypertension, postural hypotension, cardiovascular collapse and death
Central nervous system/psychiatric: anxiety, depression, psychosis, convulsions
Bulbar: Decreased ability to swallow, can lead to aspiration

9. Diagnosis Type of patient Samples to send to laboratory Sample
Suspected acute attack
Urine (30 ml)
Define the type of porphyria
EDTA blood sample (2 tubes)
Urine (30ml)
Stool sample
Skin disease
Sample
Tests done
Urine*
Enzyme quantitation
Blood*
Erythrocyte fluorescence screen, plasma porphyrin scan, DNA testing (R59W mutation for Porphyria Variegata)
Stool*
NB: All samples to be protected against light
Porphyrin and protoporphyrin quantitation (to determine type of porphyria)

10. Treatment of acute attack
Symptom to treat
Treatment
Definitive treatment of acute attack with neuropathy
Haematin arginate (NormosangTM )
3-4mg/kg/d IV x 4 days
(This works by increasing the haem pool to enhance negative feedback to ALA to reduce formation of precursors)
Might be useful in acute attack
Carbohydrates:
10% Dextrose saline
Oral carbohydrate loading – 2000 kcal/d
General treatment of acute attack
Withdraw trigger
Hydrate well
Monitor electrolytes
Abdominal pain
Codeine, morphine, pethidine

11. Treatment (cont) Nausea and vomiting Prochlorperazine
Hypertension and tachycardia
β-blockers
Psychosis
Chlorpromazine, promazine, trifluoperazine
Convulsions
Clonazepam, Lorasepam
Bulbar involvement/respiratory failure
Intubate and ventilate

12. A “safe” anaesthetic technique
Pre-operatively
Limit NPO time (prevent starvation)
Start Dextrose saline drip early if patient not
first on list
Anxiolysis (midazolam, temazepam)
Intra-operatively
Sufentanil, alfentanil, fentanyl
Propofol
Suxamethonium, pancuronium (atracurium has been used)
Halothane (sevoflurane has been used)
Neostigmine, glycopyrrolate
Post-operatively
Morphine, pethidine, codeine, paracetamol, Ibuprofen