Prevalence of Hereditary Coproporphyria
The estimated prevalence of hereditary coproporphyria (HCP) in the UK is 1–2 per million people, making it the rarest of the acute hepatic porphyrias. 1
Genetic Predisposition vs. Overt Disease
The distinction between genetic predisposition and clinically manifest disease is critical for understanding HCP prevalence:
Genetic predisposition: Using population genetic databases (GnomAD) and pathogenic CPOX variants, a rough estimate suggests approximately 1 in 4,000 individuals carry pathogenic variants predisposing to HCP 1
Overt symptomatic disease: The actual clinical penetrance is extremely low at approximately 0.4%, meaning only a small fraction of genetic carriers ever develop symptomatic disease 1
In one documented Australian family, only 1 of 22 family members with low coproporphyrinogen oxidase activity and elevated fecal coproporphyrin III:I ratio experienced a definite acute attack 1
Comparative Rarity Among Porphyrias
HCP is significantly rarer than other acute hepatic porphyrias:
Acute intermittent porphyria (AIP): Most common acute porphyria with overt disease prevalence of ~1 in 200,000 1
Variegate porphyria (VP): Overt disease prevalence of ~1 in 300,000 (though higher in South Africa due to founder effect) 1
HCP: Estimated at 1–2 per million, making it the least common 1
Clinical Implications of Low Penetrance
The extremely low penetrance has important clinical ramifications:
Most individuals carrying HCP pathogenic variants remain asymptomatic throughout their lives 1
Symptomatic attacks are almost always precipitated by known triggers including drugs (barbiturates, sulfonamides), alcohol, infections, or low caloric intake 2, 3
HCP was initially considered merely an asymptomatic biochemical abnormality when first described in 1955, though it later became evident that acute attacks similar to AIP and VP could occur 2
Important Diagnostic Considerations
Given its rarity, HCP is frequently underrecognized:
The dramatic increase in coproporphyrin III excretion (10-200 times normal) with intense red fluorescence under UV light is the specific diagnostic marker 3
During acute attacks, urinary ALA and PBG elevate similarly to other acute porphyrias, but marked elevation of fecal coproporphyrin distinguishes HCP 2
Biochemical confirmation must precede genetic testing to avoid false diagnoses in asymptomatic carriers 1
Rare Homozygous Variant
Homozygous HCP (Harderoporphyria) is exceptionally rare with only a few cases described in medical literature, typically presenting with neonatal hyperbilirubinemia, hemolytic anemia, and severe photosensitivity 4