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.

Diagnostic Criteria

Hereditary coproporphyria (HCP) is classified as both an acute (hepatic) porphyria (with neurologic manifestations that occur as discrete, severe episodes) and a chronic (cutaneous) porphyria with long-standing photosensitivity. Diagnostic criteria for HCP have been published .

Suggestive Findings

Acute hepatic porphyria should be suspected in individuals with the following symptoms or findings:

• Nausea for at least 48 hours

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with hereditary coproporphyria (HCP), the evaluations listed in are recommended (if they have not already been completed). Table 4. Recommended Evaluations Following Initial Diagnosis of Hereditary Coproporphyria Evaluation | Comment Review of medications for those thought to induce attacks | See . Detailed neurologic exam | • For signs of motor neuropathy (indicating a more advanced attack thus, need for early treatment w/hematin; see ) • Inquiry into possibility of seizures1 Measurement of serum sodium concentration | Hyponatremia is characteristic may be profound (serum sodium concentration 110 mEq/L), requiring urgent correction w/due regard for risk of central pontine myelinolysis. Quantitation of urinary excretion of PBG on several occasions over a few mos to establish baseline | For future use in determining if a new symptom or drug reaction is due to an acute attack2 Consultation w/medical geneticist /or genetic counselor | PBG = porphobilinogen 1. 2. In an acute attack urinary excretion of PBG is substantially elevated over the baseline. Treatment of Manifestations Treatment guidelines for HCP have been published (full text). Acute Attacks No curative therapy for HCP exists. Supportive therapy by multidisciplinary specialists is summarized in . Details regarding treatment with givosiran, which was approved for prophylactic treatment for individuals with HCP with frequent recurrent acute neurovisceral pain episodes (defined as more than four attacks per year) in the US, but not necessarily in all countries, follow . Table 5. Treatment of Acute Attacks in Individuals with Hereditary Coproporphyria

Surveillance Guidelines

For those who have chronically elevated ALA (which is infrequent in those who are asymptomatic) and/or are older than age 60 years, an annual assessment of liver and kidney function is recommended. Current noninvasive techniques for evaluation of fibrosis in the liver include transient elastography (FibroScan®) and a blood-based test (FibroTest® or FibroSure®) [see ]. Note: These assessments have been vetted mainly for people with chronic viral hepatitis or steatohepatitis but may also be useful in porphyria. For affected individuals older than age 60 and anyone with evidence of chronic liver injury, annual screening for hepatocellular carcinoma with abdominal imaging (e.g., ultrasound) and serum alpha-fetoprotein is indicated .