Types of Porphyria
Porphyrias are classified into eight distinct types based on the specific enzyme deficiency in the heme biosynthesis pathway, divided into acute (neurovisceral) and cutaneous categories, with some presenting mixed features. 1
Acute Hepatic Porphyrias
These disorders present with acute neurovisceral attacks characterized by severe abdominal pain, neuropsychiatric symptoms, and cardiovascular manifestations. 1
The Four Acute Porphyrias:
Acute Intermittent Porphyria (AIP): The most common acute porphyria, autosomal dominant inheritance, presents with isolated neurovisceral symptoms without skin manifestations. 2, 3 Urinary PBG remains elevated for years after acute episodes. 1
Variegate Porphyria (VP): Autosomal dominant, presents with both acute neurovisceral attacks AND bullous skin photosensitivity. 1, 2 Plasma fluorescence shows characteristic emission patterns distinct from other cutaneous porphyrias. 1
Hereditary Coproporphyria (HCP): Autosomal dominant, presents with both acute neurovisceral attacks AND bullous skin symptoms (mixed presentation). 1, 2 Coproporphyrin III is markedly elevated. 1
ALAD Deficiency Porphyria (also called Doss Porphyria or ALA Dehydratase Deficiency Porphyria): Extremely rare, autosomal recessive. 1, 3 Unique biochemical pattern with markedly elevated urinary ALA but normal or near-normal PBG, plus significantly increased coproporphyrin III. 1
Cutaneous (Non-Acute) Porphyrias
These accumulate phototoxic porphyrins causing skin damage from light exposure (400-410 nm wavelength). 1
Bullous/Blistering Cutaneous Porphyrias:
Porphyria Cutanea Tarda (PCT): The most common porphyria overall, usually sporadic (non-hereditary) in adults. 1, 2 Characterized by elevated uro- and heptacarboxyl porphyrins in urine, with hepta-, penta-, and isocoproporphyrins in feces. 1, 4, 5 Associated with hepatitis C, alcohol, iron overload, and estrogens. 4, 5
Hepatoerythropoietic Porphyria (HEP): Rare autosomal recessive form with similar porphyrin patterns to PCT but higher concentrations. 1, 4 Erythrocyte zinc-chelated protoporphyrin is typically increased. 1 Requires genetic analysis of UROD gene for confirmation. 1
Congenital Erythropoietic Porphyria (CEP): Rare, caused by uroporphyrinogen synthase deficiency. 1, 4 Characterized by increased isomer I type porphyrins in urine, feces, plasma, and erythrocytes. 1, 4 Often symptomatic in newborns. 1
Acute Photosensitivity Porphyrias:
Erythropoietic Protoporphyria (EPP): Autosomal recessive, presents with acute painful photosensitivity (not bullae). 1, 4, 2 Plasma fluorescence typically around 628 nm. 1 Most frequently symptomatic in children. 1
X-Linked Erythropoietic Protoporphyria (XLEPP): X-linked inheritance, clinically similar to EPP with acute painful photosensitivity. 1, 4 Plasma fluorescence around 628-636 nm. 4
Key Clinical Distinctions
Inheritance patterns vary critically: The three autosomal dominant acute porphyrias (AIP, VP, HCP) have low clinical penetrance, meaning pathogenic variants are frequently found in asymptomatic individuals in the general population. 1 This makes genetic testing alone inadequate for diagnosis without biochemical confirmation. 1
Timing of symptom onset differs by type: Erythropoietic porphyrias (CEP, EPP) often present in newborns or children, acute hepatic porphyrias (AIP, VP, HCP) typically manifest in early adulthood, while PCT most commonly presents in middle-aged or older adults. 1
Critical Diagnostic Pitfall
Never use genetic testing as initial diagnostic screening in symptomatic patients. 1 Biochemical testing demonstrating characteristic patterns of porphyrin precursors and porphyrins in urine, feces, and blood must be performed first to establish the diagnosis and classify the specific type. 1 Secondary porphyrin elevations from liver disease, iron deficiency, lead intoxication, and chronic kidney disease are far more common than true porphyrias and can cause diagnostic confusion. 4, 2