Hereditary Coproporphyria Workup

Updated: Mar 22, 2021
  • Author: Thomas G DeLoughery, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Approach Considerations

The diagnosis of hereditary coproporphyria is established by demonstrating excess secretion of coproporphyrins in the stool. [11] Levels of stool coproporphyrins, especially coproporphyrin type III, are markedly elevated, usually 10-200 times greater than in controls.

Levels of urine porphyrins vary, but urine coproporphyrin levels usually are also markedly elevated, especially during acute attacks of the disease. Elevated porphobilinogen levels in the presence of appropriate clinical symptoms is diagnostic of porphyria; this is true of both hereditary coproporphyria and acute intermittent porphyria (AIP). [13, 14] After symptom resolution, urinary porphobilinogen levels may return to normal relatively quickly. [14]

Mild elevations of urine coproporphyrins (eg, as high as two times the reference range) are common and nonspecific. Fasting, subtle liver disease, or normal variations are the most common causes of elevated urine coproporphyrins. In such cases, patients may be incorrectly labeled as having porphyria.

Serum sodium levels should be measured in patients experiencing attacks, as hyponatremia is common; this has been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but renal and/or gastrointestinal sodium loss may also be involved. [14] Mild leukocytosis is another nonspecific finding during an attack.

Although coproporphyria is caused by a defective enzyme, there is little use in measuring the activity of coproporphyrinogen oxidase. The vast majority of patients who have the defective enzyme do not have any symptoms of the disease. Furthermore, the only available clinical assay has been withdrawn due to problems with high rates of false-positive results. The diagnosis of a porphyria attack rests on demonstration of excessive excretion of porphyrins and porphyrin precursors.

Imaging studies are not helpful. Abdominal films sometimes demonstrate an ileus. Findings on cranial computed tomography scans are normal. Brain magnetic resonance imaging scans occasionally show signs of increased edema in patients with very severe attacks.

Identification of a heterozygous pathogenic variant in CPOX (encoding the enzyme coproporphyrinogen-III oxidase) confirms the diagnosis and enables family studies. [15]