History and exam
Key diagnostic factors
common
abdominal pain
Symptoms out of proportion to the physical exam and not explained by common causes.
Often accompanied by ileus and urinary retention.
tachycardia
Common physical finding.
hypertension
Common physical finding. Sometimes becomes chronic.[6]
dark or red urine
Urinary excretion of porphyrins and degradation products of porphobilinogen.
Other diagnostic factors
common
nausea
Accompanies abdominal pain and ileus.
vomiting
Accompanies abdominal pain and ileus.
abdominal distension
Accompanies abdominal pain and ileus.
constipation
Accompanies abdominal pain and ileus.
urinary hesitancy and dysuria
Reflects neurologic bladder dysfunction.
pain in extremities, back, and chest
Reflects peripheral nerve involvement.
proximal muscle weakness
In severe attacks. Early motor neuropathy.
painful hyperesthesia
Reflects sensory involvement, and may be manifested especially by pain in the extremities.
mental symptoms
May range from minor behavioral changes and insomnia to depression, agitation, and confusion.
seizures
Central nervous system manifestation of a porphyria attack itself or due to hyponatremia resulting often from the syndrome of inappropriate ADH secretion.
uncommon
diarrhea
Occurs in 5% to 12% of patients.[6] Less common than constipation.
quadriparesis
May occur during progression of a severe and prolonged attack, especially if diagnosis and treatment are delayed.
respiratory failure
May occur in severe, prolonged attacks due to advanced motor neuropathy causing respiratory muscle weakness. Early detection of respiratory impairment and monitoring in intensive care is often recommended.
Risk factors
strong
family history
AIP results from the autosomal dominant inheritance of a deficiency in porphobilinogen deaminase, the third enzyme in the heme biosynthetic pathway. Because penetrance is low, the family history is often negative. Very rarely, a more severe and distinct form of the disorder is inherited from both parents (homozygous disease).
female sex
Symptoms develop more commonly in women than in men.[4] This is not fully explained, although female hormones (especially progesterone) have been implicated.
drugs
Certain drugs (e.g., barbiturates, phenytoin, progestins, metoclopramide, sulfonamide antibiotics) exacerbate AIP, and most are inducers of delta-aminolevulinic acid synthase, and cytochrome P-450 enzymes in the liver.[4]
elevated progesterone levels
decreased caloric or carbohydrate intake
Restriction of calories and carbohydrate can exacerbate acute porphyrias. The mechanistic link is through hepatic delta-aminolevulinic acid synthase. Induction of this rate-controlling enzyme is enhanced by fasting and repressed by carbohydrate loading.[11][12][13] Delta-aminolevulinic acid synthase is upregulated by the peroxisomal proliferator-activated cofactor 1-alpha (PGC-1-alpha), a coactivator of nuclear receptors and transcription factors that is greatly regulated by diet and nutritional status.[13]
smoking
Smoking induces heme synthesis and cytochrome P-450 enzymes in the liver, and heavy smoking in patients with AIP has been related to more frequent attacks.[14]
weak
alcohol
Alcohol intake may exacerbate AIP though induction of delta-aminolevulinic acid synthase.
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