- Clinical science
Porphyrias are a group of inherited or (rarely) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow. All porphyrias are characterized by the accumulation of porphyrin, or intermediates of its biosynthesis, which can cause a variety of symptoms depending on the organs involved (e.g., skin, liver, CNS). Porphyria cutanea tarda (PCT) is the most common form and presents with chronic, blistering cutaneous photosensitivity and tea-colored urine. The second most common form, acute intermittent porphyria (AIP), is characterized by life-threatening attacks of severe abdominal pain, constipation, tachycardia, and neuropsychiatric abnormalities. Attacks are generally triggered by certain drugs, alcohol, infections, or fasting. The diagnosis is confirmed by detecting metabolic heme precursors in urine, which often appear reddish. An important acquired form of porphyria is lead poisoning, which is discussed in another learning card (see ). Patients with a known porphyria should avoid potential triggers. Management consists of supportive care; acute attacks should be treated with hemin to reduce heme production.
- Porphyrias are a group of inherited or (rarely) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow.
- (Trigger →) ↓ enzyme activity in heme biosynthesis → intermediates of heme production accumulate
- → Deposited into different tissue, such as the skin and/or liver → symptoms
- → Increased urinary elimination → metabolite detection
- The specific intermediates that accumulate depends on which enzymes are affected in the heme biosynthesis pathway.
Porphyrias can be classified based on inheritance or organ of accumulation.
- Inheritance: primary (inherited) or secondary (acquired)
Organ of accumulation:
- Hepatic (more common)
- Acute (often systemic): AIP is most common
- Chronic (often cutaneous): PCT is most common
- Erythropoietic variants (rare)
- Hepatic (more common)
Primary porphyrias (hereditary enzyme defect)
- Hepatic porphyrias
- Acute hepatic porphyrias
- Chronic hepatic porphyrias
- Erythropoietic porphyrias
Secondary porphyria (acquired)
- Secondary coproporphyria (caused by e.g., intoxication, hepatic diseases, blood disorders, infections, starvation)
- Secondary protoporphyrinemia; (caused by e.g., anemia, alcohol, or chronic heavy metal poisoning)
- Most common porphyria
- Peak incidence: 40–70 years
- Sex: ♂ > ♀
- Defective uroporphyrinogen III decarboxylase (UROD)
- Susceptibility factors
- Sunlight exposure
- Cutaneous manifestations
- Commonly occurs on:
- Dorsum of the hand
- Face and neck
- Extensor surface of the forearm
- Avoid susceptibility factors and excessive sunlight
- Second most common porphyria
- Peak incidence: ∼ 30 years
- Sex: ♀ > ♂ (2:1)
Attacks are triggered by:
- Certain drugs (especially inducers of hepatic CYPs): Several enzymes involved in heme biosynthesis are the CYP enzymes of cytochrome P450. Inducers of CYPs stimulate heme biosynthesis resulting in the accumulation of porphyrin intermediates.
- Sex hormones, especially progesterone
- Fasting: Increased intake of carbohydrates may alleviate symptoms.
- Stress (e.g., surgery, infection)
- Pathophysiology: defective PBG-D → accumulation of porphobilinogen (PBG) and δ-aminolevulinic acid (ALA) → symptoms
- GI symptoms: severe abdominal pain, nausea, vomiting
- Neurological abnormalities
- Psychiatric abnormalities; : hallucinations, disorientation, anxiety, insomnia
- Autonomic dysfunction; : tachycardia; , hypertension
- Red-purple urine
- In contrast to some porphyrias, the skin is not involved
The skin is not involved!
The 5 P's: Painful abdomen, Polyneuropathy, Psychologic disturbances, Purple pee, Precipitated by triggers like drugs