History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include family history of acute porphyria, female gender, nutritional alterations (e.g., fasting, dieting), intercurrent illness, and exposure to drugs or hormones known to provoke attacks of AIP.

abdominal pain

Symptoms out of proportion to the physical examination 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 neurological bladder dysfunction.

pain in extremities, back, and chest

Reflects peripheral nerve involvement.

proximal muscle weakness

In severe attacks. Early motor neuropathy.

painful hyperaesthesia

Reflects sensory involvement, and may be manifested especially by pain in the extremities.

mental symptoms

May range from minor behavioural changes and insomnia to depression, agitation, and confusion.

seizures

Central nervous system manifestation of a porphyria attack itself or due to hyponatraemia resulting often from the syndrome of inappropriate ADH secretion.

uncommon

diarrhoea

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 haem 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

Elevated progesterone levels during the luteal phase appear to be correlated to cyclic attacks. Some metabolites of progesterone and testosterone can also be implicated in causing attacks.[4][10]

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 co-factor 1-alpha (PGC-1-alpha), a co-activator of nuclear receptors and transcription factors that is greatly regulated by diet and nutritional status.[13]

smoking

Smoking induces haem synthesis and cytochrome P-450 enzymes in the liver, and heavy smoking in patients with AIP has been related to more frequent attacks.[14]

age >13 years

Symptoms of this inherited disease are rare before puberty.[3][4]

weak

alcohol

Alcohol intake may exacerbate AIP though induction of delta-aminolevulinic acid synthase.

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