Acute Porphyrias
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Direct answer
Acute porphyrias are inherited defects in haem synthesis that cause neurovisceral attacks, and acute intermittent porphyria is the most important member. An attack typically produces severe colicky abdominal pain without peritonism, neuropsychiatric change, autonomic instability and sometimes a motor neuropathy, while urine darkens on standing in light. The diagnosis is made by raised urinary porphobilinogen during an attack, and treatment is intravenous haem, carbohydrate loading and withdrawal of precipitating drugs.
What you must remember
- Acute intermittent porphyria: Hydroxymethylbilane synthase (porphobilinogen deaminase) deficiency, inherited in an autosomal dominant pattern with incomplete penetrance.
- Abdominal pain: The commonest attack feature, severe and colicky, with vomiting and constipation, usually without peritonism.
- Neuropathy: Motor and often proximal, sometimes progressing to respiratory weakness; autonomic involvement brings tachycardia, hypertension and hyponatraemia.
- Urine colour: Porphobilinogen darkens on exposure to light, so urine may look normal when first passed and dark only after standing.
- Precipitants: Barbiturates, phenytoin, carbamazepine, sulphonamides, oestrogens and progestogens, and fasting or crash dieting.
- Haem therapy: Intravenous haem arginate or haemin for moderate to severe attacks, usually given for several days alongside glucose.
- Prevention: Givosiran, a subcutaneous small interfering RNA targeting ALAS1, reduces attack frequency in recurrent cases.
An attack that looks like a surgical abdomen
A 27-year-old woman has three days of colicky central abdominal pain, vomiting and constipation, with diffuse tenderness without guarding and unremarkable imaging. Over the next day she develops tachycardia, a blood pressure of 170/100 mmHg and a sodium of 128 mmol/L, then weakness in both arms that rises towards the shoulders.
Acute porphyria should be suspected when a dramatic abdominal illness has no surgical lesion and autonomic or neurological features appear.
- Spot urine: Collect a porphobilinogen sample before treatment and protect it from light, since porphobilinogen degrades in light.
- Confirm during the attack: A raised level confirms acute porphyria, and her serum sodium and respiratory function need close monitoring.
- Stop precipitants: Stop all precipitating drugs, including her oral contraceptive.
- Glucose: Give intravenous glucose to suppress hepatic haem synthesis.
- Haem: Haem arginate is given for several days.
- Analgesia: Opioids are used for pain while barbiturates are avoided, and antiemetics are chosen with care.
- Family screening: First-degree relatives need testing, because penetrance is incomplete and early identification allows prevention of future attacks.
Where the exam tries to catch you
Four traps recur in examinations on acute porphyria.
- Trap: treating dark urine as the confirmation. Correct: dark urine prompts the diagnosis but does not confirm it; the porphobilinogen test is confirmatory and can be normal between attacks.
- Trap: confusing acute porphyria with porphyria cutanea tarda. Correct: porphyria cutanea tarda, a uroporphyrinogen decarboxylase deficiency, causes photosensitive skin blistering and is linked to alcohol, hepatitis C and iron overload.
- Trap: missing lead poisoning. Correct: lead inhibits haem synthesis enzymes and produces colicky pain, anaemia and neuropathy; blood lead level and basophilic stippling help separate the two.
- Trap: reaching for barbiturates or sulphonamides in a known porphyric patient. Correct: they are unsafe drugs, barbiturates being potent enzyme inducers, that can precipitate an attack, however convenient they seem for sedation or infection.
Frequently asked questions
Which test diagnoses acute intermittent porphyria during an attack?
Raised urinary porphobilinogen during an acute attack is the key test for acute intermittent porphyria. It is best measured quantitatively on a fresh, light-protected spot urine sample, and a normal result between attacks does not exclude the disorder.
Why must barbiturates be avoided in acute porphyria?
Barbiturates induce hepatic cytochrome P450 enzymes and increase aminolevulinic acid synthase activity, which precipitates acute porphyric attacks. Phenytoin, sulphonamides and oestrogens are other precipitants, so a drug safety check is part of every acute porphyria evaluation.
How does haem therapy help in acute porphyria?
Intravenous haem arginate or haemin suppresses hepatic aminolevulinic acid synthase, reducing the build-up of toxic precursors during an acute attack. It is given for several days alongside glucose and works best when started early in the attack.
How does acute porphyria differ from porphyria cutanea tarda?
Acute porphyrias cause neurovisceral attacks with abdominal pain and neuropathy, whereas porphyria cutanea tarda causes chronic photosensitive skin blistering from uroporphyrin accumulation. Porphyria cutanea tarda responds to phlebotomy or low-dose chloroquine, whereas acute attacks need haem and a review of precipitating drugs.
Which condition mimics acute porphyria with abdominal pain and neuropathy?
Lead poisoning mimics acute porphyria with colicky abdominal pain, anaemia and peripheral neuropathy, since lead inhibits haem synthesis enzymes such as aminolevulinic acid dehydratase. Blood lead level and basophilic stippling of red cells help distinguish lead poisoning from acute intermittent porphyria.