Diagnosis of Porphyria

The porphyrias are disorders of heme synthesis, which has eight steps. Each type of porphyria involves a defect, either inherited or acquired, in a pathway enzyme. When the defect is physiologically significant, it results in overproduction of pathway precursors preceding the defective step which enter the circulation and are excreted into urine or bile. The diseases have been grouped as acute hepatic porphyrias and photocutaneous porphyrias. The acute porphyrias are due to hepatic overproduction of the porphyrin precursors, delta aminolevulinic acid and porphobilinogen, and the symptoms are caused by injury primarily to the nervous system. Cutaneous porphyria is due to overproduction of photosensitizing porphyrins by the liver or bone marrow, depending on the type of porphyria.

Principal Types of Porphyria

Feature Acute Intermittent Porphyria Porphyria Cutanea Tarda Protoporphyria
Tissue site Liver Liver Bone marrow
Manifestations Pain in the abdomen and back and nausea, both of which increase over a few days; tachycardia without fever; seizures (in 20% of patients) Slow onset of painless blisters, fragile skin, scars, hypertrichosis on sun-exposed skin Rapid onset of pain, edema, and itching after sun exposure; thickening of perioral skin and skin over the knuckles with repeated exposure
Age at onset and sex 18–45 yr; 90% female predominance >40 yr; male predominance 1–3 yr (although delayed diagnosis is common); equal male–female incidence
Color of urine Normal to dark amber Brown or reddish brown Normal
Associated conditions, environmental factors Use of cytochrome P-450–inducing medications or oral contraceptive pills, severely restricted caloric intake Hepatitis C virus infection, human immunodeficiency virus infection, iron overload, use of alcohol, use of estrogen History of gallstones, microcytic anemia, cholestasis
Skin lesions None Painless blisters on sun-exposed skin, shallow open sores, depigmented scars Acute injury: erythema and mild edema; chronic injury: lichenified skin over knuckles and around mouth

 
Heme Pathway Intermediates in the Diagnosis of Porphyria

Pathway Intermediate Porphobilinogen in urine (mg/g of creatinine) Uroporphyrin in urine (ug/g of creatinine) Protoporphyrin in blood (ug/dl)
Reference Range 0-2 0-30 0-80
Asymptomatic Acute Intermittent Porphyria 1-10** <3
Acute Intermittent Porphyria during Attack 20-300 20-200
Porphyria Cutanea Tarda without Symptoms (Treated) <2 30-300
Active (Untreated) Porphyria Cutanea Tarda <4 >500
Protoporphyria >400

 
To convert the values for porphobilinogen to micromoles per day, divide by 0.226. To convert the values for uroporphyrin to nanomoles per day, divide by 0.831. To convert the values for blood protoporphyrin to nanomoles per deciliter, divide by 0.563.
** In a minority of asymptomatic carriers, the level of urine porphobilinogen is higher than 10 mg per gram of creatinine. The risk of an attack is increased, relative to the risk when the baseline porphobilinogen level is normal or only slightly elevated.
 
References:

  1. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862-872. [Medline]
  2. Karim Z, Lyoumi S, Nicolas G, Deybach JC, Gouya L, Puy H. Porphyrias: A 2015 update. Clin Res Hepatol Gastroenterol. 2015 Sep;39(4):412-25. [Medline]

 
 
Created Oct 13, 2017.

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