Acute intermittent porphyria

Also known as AIP.
Many historians believe that this condition is a potential explanation for "the madness of King George".

AIP causes acute intermittent attacks of symptoms. An attack can result in permanent disability or death.

 

Pathophysiology

In AIP there is a defective porphobilinogen deaminase gene. This results in accumulation of porphobilinogen in the cytoplasm, causing neurotoxic effects. The CNS is relatively protected due to the blood-brain barrier. The autonomic and peripheral nervous system are vulnerable, resulting in abdominal pain, tachycardia, paresis etc. 

 

Features of an acute attack

• Gastrointestinal
• Abdominal pain
• Vomiting 
• Constipation 
• Neuropsychiatric
• Peripheral neuropathy
• Seizures
• Psychosis 
• Cardiovascular
• Hypertension
• Tachycardia
• Shock
• Other
• Fever
• Hyponatraemia
• Hypokalaemia
• Proteinuria
• Urinary porphobilinogens
• Discoloured urine 

• Rarely
• Bulbar paralysis
• Respiratory paralysis 

 

Genetics

• Low-penetrance autosomal dominant 
• Porphobilinogen deaminase gene
• 28% have no family history (caused by de novo mutations) 
• 10% with the defective gene have neurovisceral symptoms

 Triggers

• Infection
• Starvation, nil by mouth
• Reproductive hormones (pregnancy, pre-menstrual) 
• Smoking 
• Anaesthesia
• Cytochrome P450 enzyme inducers
• Disruptions of porphyrin metabolism
• Alcohol
• Lead poisoning
• Iron deficiency
• Drugs
• Diclofenac
• Alcohol
• Oral contraceptive pill & HRT
• Tricyclic antidepressants
• Benzodiazepines
• Anaesthetic agents (barbituates, halothane) 
• Antibiotics (cephalosporins, sulphonamides, macrolides, tetracyclines, rifampicin, trimethoprim, chloramphenicol, metronidazole). 
• Metoclopramide
• ACE-inhibitors
• Ca ²⁺ channel blockers
• Statins
• Anticonvulsants
• Furosemide
• Sulphonylureas
• Lidocaine
• Gold salts
• Antihistamines
• Amphetamines

 

Epidemiology

• Attacks are more common in women
• Attacks are more common in those aged 18-40
• This is the most common form of porphyria
• Prevalence in UK: 1-2 per 100,000 

 

Diagnostics

• During an attack, urine porphobilinogen is raised. The urine may turn deep red on standing. 
• In 50%, urine porphobilinogen is raised between attacks.
• Faecal porphyrin levels are normal.
• No cutaneous photosensitivity. 
• Beware: Can mimic acute surgical abdomen (colic, vomiting, fever, leukocytosis). Anaesthesia use (for surgery) could cause a disaster. 

 

Management of an acute attack

• Remove precipitants
• IV fluids to correct electrolyte imbalance
• High carbohydrate intake
• IV haematin to inhibit porphyrin synthesis.
• Nausea control with prochlorperazine
• Sedation with chlorpromazine 
• Pain control with opiate or opioid analgesia (avoid oxycodone)
• Seizure control with diazepam
• Tachycardia and hypertension treatment with a beta-blocker

 

Long-term management

• Avoid triggers
• Medical identification tag: wrist bracelet, neck pendant and/or card, to warn medics about porphyria. 
• Genetic counselling