eMedicine Specialties > Hematology > Heme Synthesis and Disorders

Porphyria, Hereditary Coproporphyria

Author: Thomas G DeLoughery, MD, Professor of Medicine and Pathology, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health Sciences University
Contributor Information and Disclosures

Updated: Nov 4, 2009

Introduction

Background

Coproporphyria is one of the porphyrias, a group of diseases that involves defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. Coproporphyria manifests with abdominal pain, neuropathies, constipation, and skin changes.

Recent research

In a retrospective analysis of 467 patients, Whatley et al examined the diagnostic accuracy of plasma fluorescence scanning, fecal porphyrin analysis, and porphobilinogen deaminase (PBGD) assay in differentiating between coproporphyria, acute intermittent porphyria (AIP), and variegate porphyria (VP).¹ The authors determined that the specificity and sensitivity of the fecal coproporphyrin isomer ratio and of the fluorescence emission peak's wavelength were great enough to differentiate between the 3 conditions. They also found that in mutation-negative patients, the accuracy of deoxyribonucleic acid (DNA) analysis followed by PBGD assay was greater than that for either test individually, in the diagnosis or exclusion of AIP.

Pathophysiology

Coproporphyria is an autosomal dominant disease that results from defects in the enzyme coproporphyrinogen oxidase. This enzyme speeds the conversion of coproporphyrinogen to protoporphyrinogen. In coproporphyria, the porphyrin precursors porphobilinogen and amino-levulinic acid (ALA) accumulate, as well as the formed porphyrin coproporphyrin. The predominant problem is neurologic damage that leads to peripheral and autonomic neuropathies and the psychiatric manifestations. In coproporphyria, skin disease also is present but not as commonly as the neurovisceral symptoms.

The etiology of the skin disease may be the deposition of formed porphyrins in the skin that react with sunlight and lead to skin damage. Although patients with acute neurovisceral attacks always have elevations of porphobilinogen and ALA, researchers still are unclear about how this leads to the symptomatic disease because most patients with the genetic defect have excessive porphyrin secretion but no symptoms.²

Frequency

United States

Coproporphyria is 20 times less common (ie, 1-4 cases per 1,000,000 people) than AIP.

Mortality/Morbidity

Researchers feel that coproporphyria is a less severe disease than AIP, but deaths have been reported in improperly treated cases.

Sex

Researchers feel that women with coproporphyria tend to be symptomatic more than men are, but the data are sparse.

Age

Most patients with porphyria become symptomatic at age 18-40 years. Attacks are rare before puberty or after age 40 years.

Clinical

History

Coproporphyria displays both neurovisceral and skin manifestations.

• Neurovisceral symptoms
  • These symptoms consist of autonomic neuropathies (constipation, colicky abdominal pain, vomiting, hypertension), peripheral neuropathy, seizures, delirium, coma, and depression.
  • The sequence of events in attacks usually is abdominal pain then psychiatric symptoms (eg, hysteria), then peripheral neuropathies.
  • Patients can have very severe abdominal pain that lasts for several days. Pain of short duration (minutes) or chronic abdominal pain does not develop in coproporphyria. The pain often is epigastric and is colicky in nature.
  • The exact mechanism by which the porphyrin precursors lead to these symptoms is unknown.
  • Patients often are free of pain between attacks. Constipation is common and can be very severe. Nausea and vomiting frequently are present.
• Skin manifestations
  • The skin disease is similar to porphyria cutanea tarda. With long-term (not acute) sun exposure, patients can develop vesicals and bullae.
  • If patients are symptomatic with coproporphyria, they tend to have neurovisceral symptoms rather than skin symptoms.
• Blisters form in sun-exposed areas and can evolve into chronic scarred areas of fragile skin.
• Patients also may develop excessive hair growth in sun-exposed areas.
• Neurologic manifestations
  • Patients with coproporphyria can have central nervous system signs, including seizures, mental status changes, cortical blindness, and coma.
  • Patients often experience peripheral neuropathies that predominantly are motor neuropathies and can mimic Guillain-Barré syndrome. The weakness usually starts in the lower limbs and ascends, but neuropathies occur in any nerve distribution.
  • Diffuse pain, especially in the upper body, can be observed. Patients also can develop autonomic neuropathies, including hypertension and tachycardia.
• Psychiatric manifestations
  • Patients can have a wide variety of psychiatric symptoms.
  • Patients usually have concurrent neurologic or abdominal symptoms.

Physical

• Vital signs
  • Tachycardia develops in 30-80% of patients.
  • Fever can be present in some patients.
  • Hypertension develops in 50% of cases and may persist between attacks.
• Neurologic manifestations
  • Typically, the neuropathy is a motor neuropathy that is more predominant in the lower limbs.
  • Areflexia is observed during the examination; however, any nerve can be involved. Cranial neuropathies also are observed, and the patient may have cortical blindness.
• Abdominal manifestations: Despite the intense pain, the findings on abdominal examination often are nonspecific.
• Skin manifestations
  • Patients can have blisters, chronic erosion, and areas of excessive hair growth.
  • Skin damage develops in sun-exposed areas of the skin.

Causes

Like AIP, coproporphyria is due to a combination of a genetic enzyme defect and acquired causes that become symptomatic in rare cases.³ In patients with coproporphyria, the function of coproporphyrinogen oxidase is only 40-60% of normal.⁴ Also, like AIP, most patients with defects in coproporphyrinogen oxidase never have any symptoms. The classic inducers of porphyria are chemicals or situations that boost heme synthesis. This includes fasting and many medications.

Although extensive lists of safe and unsafe drugs exist, many of these are based on anecdotes or laboratory evidence rather than meeting strict criteria. In general, drugs that lead to increased activity of the hepatic P450 system (eg, phenobarbital, sulfonamides, estrogens, alcohol) are associated with porphyria. A large and detailed list, shown below, is available at Porphyria: A Patient's Guide. Fasting for several days also can trigger an attack. Many attacks will occur, however, without any obvious provocation.

Table 1. Drugs Thought Safe in Porphyria*

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*Bracketed [ ] drugs are those in which experimental evidence of porphyrin genicity is conflicting.

Table 2. Drugs Thought Unsafe in Porphyria^†

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*These drugs have been associated with acute attacks of porphyria.

†Bracketed [ ] drugs are those in which experimental evidence of porphyringenicity is conflicting.

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