High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria

Abstract

Hereditary coproporphyria (HCP) is the rarest of the autosomal dominant acute porphyrias with an estimated incidence of 0.02 per 10 million per year. HCP has been considered to be mild in presentation compared with the more common acute intermittent porphyria although there is limited information comparing the subtypes. Penetrance in the acute porphyrias is low with 90% of patients with a mutation never exhibiting symptoms. We present seven members from a family with HCP with a novel mutation in whom penetrance and severity are high. In addition, they appear to have a high rate of veno‐thromboembolism. Penetrance is confirmed at 57% but is suspected to be 71%. The first patient experienced life‐threatening complications, four of the seven have had recurrent attacks and the development of opioid dependence has complicated management. The case series documents the impact of a new mRNA interference molecule givosiran as well as a plan for embryo selection which is not commonly used in porphyria. The use of ketamine for the treatment of acute attacks is also documented for the first time in the porphyria literature. The use of international registries would aid the characterisation and management of this very rare disease.

Endothelial Dysfunction in Acute Hepatic Porphyrias

“…Even though acute neurovisceral attacks are the most dramatic, and potentially life-threatening, clinical manifestations of acute porphyrias, patients affected by this group of diseases do suffer from chronic complications, which may be debilitating and have a considerable impact on their quality of life. In particular, patients with symptomatic AHPs are prone to develop long-term complications of vascular nature, such as arterial hypertension, chronic kidney disease (often termed porphyria-associated kidney disease-PAKD) [ 11 , 13 , 17 , 38 , 39 ], and thrombotic events [ 40 , 41 ]. Therefore, it could be reasonably conjectured a direct involvement of the endothelium, which could be a primary site of organ damage, in the pathogenesis of AHPs.…”

Understanding Hepatic Porphyrias: Symptoms, Treatments, and Unmet Needs

“…40,52 A recent study investigating seven cases of HCP from a single family with a novel mutation found evidence contrasting current literature including a notably high disease penetrance, high rate of severe, recurrent attacks, and a high incidence of venous thromboembolism, a phenomenon not known to be associated with acute porphyria. 53…”