Porphyria cutanea tarda: bridging cellular mechanisms and laboratory approaches – a narrative review

Abstract

Porphyria cutanea tarda (PCT) is the most prevalent subtype of porphyria, a group of rare disorders caused by defects in the heme biosynthesis pathway. This narrative review highlights the current insights into the cellular and molecular mechanisms underlying PCT, linking genetic predispositions, environmental triggers, and diagnostic challenges. The pathogenesis of PCT primarily involves the deficient activity of uroporphyrinogen decarboxylase (UROD) enzyme, leading to porphyrin accumulation and subsequent oxidative stress, particularly within hepatic and mitochondrial systems. Key contributing factors include iron overload, excessive alcohol consumption, chronic viral infections (e.g., hepatitis C virus and human immunodeficiency virus), oestrogen exposure, and genetic susceptibility, in the presence of pathogenic variant of the UROD gene. Clinically, PCT is presented with photosensitive cutaneous manifestations and may be associated with underlying liver involvement, necessitating a comprehensive diagnostic evaluation. The review further outlines the critical role of laboratory diagnostics, including porphyrin profiling, and genetic testing, and emphasises the importance of multidisciplinary approaches for accurate diagnosis and management. The proposed future research direction shall focus on novel diagnostic techniques, molecular therapies, and the standardisation of clinical protocols to improve patient outcomes. This review aims to bridge the gap between cellular pathophysiology and laboratory practices, offering a comprehensive perspective for clinicians and laboratory specialists managing these rare but significant disorders.