PORPHYRIADr S Spijkerman

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

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:

1. Induction of ALA synthase activity → ↑ formation of precursors → accumulation due to genetically deficient enzyme (can’t cope with ↑ load).

2. Increase in haem demand, thus decreasing the haem pool and reducing the negative feedback on ALA synthase.

Haem pathway

Triggers

Table 1. Triggers of acute porphyric attacks

StressInfectionAlcohol StarvationDehydration MenstruationDrugs – see table 2

Table 2: Drugs Indication UWC UWEC AvoidAnaesthesia Thiopentone

EtomidateAnalgesics Tramadol

Mefenamic acidDiclofenacKetorolacPentazocineTilidine

Sedatives/anticonvulsives

Diazepam Phenobarbitone

Antibiotics ClindamycinMetronidazole

SulphonamidesErythromycinCo-trimoxazoleChloramphenicol

Local anaesthetics - - -Asthma AminophyllineAntiemetics Metoclopramid

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Clinical presentation Chronic types cause skin reactions

(bullae, rash etc) → not life threatening

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

DiagnosisType of patient Samples to send to

laboratorySuspected acute attack Urine (30 ml)Define the type of porphyria

1. EDTA blood sample (2 tubes)

2. Urine (30ml)

3. Stool sample

Skin disease 1. EDTA blood sample (2 tubes)

2. Urine (30ml)Sample Tests doneUrine* 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)

Treatment of acute attackSymptom to

treatTreatment

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:1. 10% Dextrose

saline2. Oral carbohydrate

loading – 2000 kcal/d

General treatment of acute attack

Withdraw triggerHydrate wellMonitor electrolytes

Abdominal pain Codeine, morphine, pethidine

Treatment (cont)

Nausea and vomiting ProchlorperazineHypertension and tachycardia β-blockers

Psychosis Chlorpromazine, promazine, trifluoperazine

Convulsions Clonazepam, Lorasepam

Bulbar involvement/respiratory failure

Intubate and ventilate

A “safe” anaesthetic techniquePre-operatively Limit NPO time (prevent

starvation)Start Dextrose saline drip early if patient not first on listAnxiolysis (midazolam, temazepam)

Intra-operatively Sufentanil, alfentanil, fentanylPropofolSuxamethonium, pancuronium (atracurium has been used)Halothane (sevoflurane has been used)Neostigmine, glycopyrrolate

Post-operatively Morphine, pethidine, codeine, paracetamol, Ibuprofen