Clinical Guidance

Hereditary coproporphyria (HCP) is classified as both an acute and a chronic porphyria. Porphyrias with neurologic manifestations are considered acute, because the symptoms occur as discrete, severe episodes. Porphyrias with cutaneous manifestations are considered chronic, because photosensitivity is long standing . In a German study of 46 individuals with acute HCP, 90% had abdominal pain; only 13% had cutaneous findings despite substantial overproduction of coproporphyrin . An earlier British study of 111 individuals with HCP reported similar findings . Symptoms prior to puberty in individuals who are heterozygous for a CPOX pathogenic variant have never been observed. Fertility and longevity do not appear to be reduced in CPOX heterozygotes.

Acute Attacks

The initial symptoms of an acute ...

Source: GeneReviews — "Hereditary Coproporphyria"

Penetrance

Because population studies to determine the prevalence of HCP heterozygosity have not been done, the penetrance of CPOX pathogenic variants is unknown. Given the rarity of acute attacks of HCP relative to acute intermittent porphyria (AIP), it is suspected that only a small minority of CPOX heterozygotes express the clinical disease. In 32 members of an Australian family, 14 (including 10 adults) were determined to have HCP on the basis of a high fecal COPRO III/I ratio and/or low lymphocyte CPOX enzyme activity; however, only one had clinical symptoms of porphyria . HCP, along with AIP and VP, are genetic disorders with reduced penetrance. Heme production in most heterozygotes appears to be adequate for physiologic homeostasis.

Source: GeneReviews — "Hereditary Coproporphyria"

Differential Diagnosis

The genetic porphyrias comprise a group of distinct diseases, each resulting from alteration of a specific step in the heme synthesis pathway that results in accumulation of a specific metabolite. In the porphyrias are grouped by their principal clinical manifestations (neurovisceral or cutaneous) and the tissue origin of the excess production of pathway intermediates (liver [i.e., hepatic] or bone marrow [i.e., erythropoietic]). • Porphyrias with neurovisceral manifestations are considered acute because the symptoms occur as discrete, severe episodes, which may be spontaneous but frequently are induced by external factors. The four acute porphyrias are: ALA dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), HCP, and variegate porphyria (VP). Only a few individuals with ADP have been reported in the world literature. • Porphyrias with cutaneous manifestations include either chronic blistering skin lesions (i.e., VP as well as PCT, HCP, CEP, and hepatoerythropoietic porphyria [HEP]) or acute non-blistering photosensitivity (i.e., EPP and XLP). Table 3. Classification of the Hereditary Porphyrias

Source: GeneReviews — "Hereditary Coproporphyria"

Clinical Guidance

Avoid the following:

• Extreme caloric deprivation (i.e., total fasting, gastric bypass surgery). A case report of an acute attack occurring in a 23-year-old male who had been taking Hydroxycut®, an over-the-counter weight loss supplement, has been published .

• Female reproductive hormones. For recommendations regarding contraception, see .

• Medications. Some drugs are clearly unsafe for CPOX heterozygotes. It is important to note, however, that many other drugs are safe. Providers should not regard individuals with acute porphyria as "untreatable." Compilations of safe and unsafe drugs are available online and are updated as new information becomes available. See porphyriafoundation.org, drugs-porphyria.org, or the smartphone app found at porphyriadrugs.com.

In theory, the most dangerous medications are inducers of CYPs, such as barbiturates and the related compound, phenytoin.

Source: GeneReviews — "Hereditary Coproporphyria"

Therapies Under Investigation

Hematin for infusion (Panhematin®, Recordati Group) is currently the only approved therapy for symptomatic acute porphyria and is a critical part of management. However, it has shortcomings: poor stability in solution; the need for intravenous administration with the attendant risk of phlebitis; interference with coagulation; and iron overload. Alternatives are under investigation. One is gene therapy in which the normal gene (CPOX in the case of hereditary coproporphyria) is targeted to hepatocytes (ClinicalTrials.gov Identifier NCT02082860). Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Hereditary Coproporphyria"