Acute intermittent porphyria (AIP) is a rare autosomal dominant inherited disorder characterised by a partial deficiency of porphobilinogen deaminase, which leads to the accumulation of porphyrin precursors and porphyrins in the body.
Most individuals remain asymptomatic, but symptoms can be triggered by use of certain drugs, steroid hormones, or alteration of nutritional status.
The most common presenting features include pain in the abdomen, extremities, back, and chest; tachycardia; hypertension; nausea and vomiting; constipation; and peripheral motor neuropathy.
The pain is neuropathic and is not accompanied by inflammation.
Red or brownish urine results from marked increases in urinary excretion of haem pathway intermediates. Porphyrins are reddish and fluoresce when exposed to long-wave ultraviolet light. Porphobilinogen is colourless but degrades on standing to form porphyrins and brownish pigments.
AIP is a rare genetic disorder characterised by a partial deficiency of porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase, the third enzyme in the haem biosynthetic pathway. When exacerbating factors induce haem biosynthesis, the hepatic enzyme delta-aminolevulinic acid (ALA) synthase is upregulated. This stimulates increased production of ALA and porphobilinogen (PBG). Because patients with AIP have a partial deficiency of PBGD, which is downstream of ALA synthase in the haem biosynthesis pathway, they cannot convert all of the ALA and PBG into hydroxymethylbilane, the next compound in the haem biosynthesis pathway. Consequently, the porphyrin precursors ALA and PBG accumulate in the body. Urinary excretion of ALA, PBG, and porphyrins is increased when this occurs.
More than 400 mutations of the gene encoding PBGD have been identified in different AIP families. Most of those who inherit one copy of these mutations remain asymptomatic with little or no elevation in ALA, PBG, and porphyrins, but the condition can be activated after puberty by some drugs and steroid hormones (especially progestins) or by reducing dietary calorie intake.
History and exam
Key diagnostic factors
- presence of risk factors
- abdominal pain
- dark or red urine
Other diagnostic factors
- abdominal distension
- urinary hesitancy and dysuria
- pain in extremities, back, and chest
- proximal muscle weakness
- painful hyperaesthesia
- mental symptoms
- respiratory failure
- family history
- female sex
- elevated progesterone levels
- decreased caloric or carbohydrate intake
- age >13 years
1st investigations to order
- urinary porphobilinogen (PBG) and total porphyrins
- serum PBG
Investigations to consider
- delta-aminolevulinic acid (ALA)
- plasma total porphyrins (including plasma fluorescence scanning)
- urinary porphyrins using high-performance liquid chromatography (HPLC)
- faecal total porphyrins (if elevated, fractionation of individual porphyrins by HPLC)
- faecal porphyrins using HPLC
- erythrocyte porphobilinogen deaminase activity
- porphobilinogen deaminase/hydroxymethylbilane synthase gene sequencing
- serum sodium levels
- CT or MRI brain
mild acute attack
severe acute attack
recurrent non-cyclic attacks
women with frequent recurrent cyclic attacks
non-responsive to medical therapy
- Other conditions that cause abdominal pain
- Delta-aminolevulinate dehydratase deficiency porphyria
- Hereditary coproporphyria
- Emergency room guidelines for acute porphyrias
- Diagnosis of the porphyrias
- Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer