Pathogenesis and clinical management of liver damage in porphyrias: Mechanisms and therapeutic approaches

Table 1 Classification, genetic basis, and clinical features of major porphyria subtypes

Porphyria type	Enzyme deficiency	Gene	Inheritance	Primary site of synthesis	Accumulated porphyrin intermediate	Neurovisceral symptoms	Cutaneous symptoms	Liver involvement
Acute hepatic porphyrias
ADP	ALA-dehydratase	ALAD	AR	Liver	ALA	+	-/+	-
AIP	PBG deaminase	HMBS	AD	Liver	ALA, PBG	++	-	-
HCP	Coproporphyrinogen oxidase	COPROX	AD	Liver	ALA, PBG, coproporphyrin III	+	+	-
VP	Protoporphyrinogen oxidase	PROTOX	AD	Liver	ALA, PBG, coproporphyrin III, protoporphyrin IX	+	+	+
Hepatic cutaneous porphyrias
PCT	Uroporphyrinogen decarboxylase	UROD	AD/sporadic	Liver	Urinary porphyrins, carboxylated porphyrin	-	++	+
HEP	Uroporphyrinogen decarboxylase	UROD	AR	Liver	Urinary porphyrins, carboxylated porphyrin	-	++	+
Erythropoietic cutaneous porphyrias
CEP	Uroporphyrinogen III synthase	UROS	AR	Bone marrow	Urinary porphyrin 1, fecal porphyrin I	-	++	-
EPP	Ferrochelatase	FECH	AR	Bone marrow	Protoporphyrin IX	-	++	+
XLP	ALA synthase 2	ALAS2	X-linked	Bone marrow	Protoporphyrin IX, Zn-bound protoporphyrin IX	-/+	+	+

AD: Autosomal dominant; AR: Autosomal recessive; ALA: Δ-aminolevulinic acid; PBG: Porphobilinogen; EPP: Erythropoietic protoporphyria; XLP: X-linked protoporphyria; AIP: Acute intermittent porphyria; UROD: Uroporphyrinogen decarboxylase.