Biomaterial Database

How I treat erythropoietic protoporphyria and X-linked protoporphyria. 2023

Rebecca Karp Leaf, and Amy K Dickey

Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA.

Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by reduced expression of ferrochelatase, the enzyme that catalyzes the final step in heme biosynthesis. The resultant accumulation of protoporphyrin IX leads to severe, painful cutaneous photosensitivity, as well as potentially life-threatening liver disease in a small percentage of patients. X-linked protoporphyria (XLP) is clinically similar to EPP but results from increased activity of δ-aminolevulinic acid synthase 2, the first step in heme biosynthesis in the bone marrow, and also causes protoporphyrin accumulation. Although historically the management of EPP and XLP (collectively termed protoporphyria) centered around avoidance of sunlight, novel therapies have recently been approved or are in development, which will alter the therapeutic landscape for these conditions. We present 3 patient cases, highlighting key treatment considerations in patients with protoporphyria, including (1) approach to photosensitivity, (2) managing iron deficiency in protoporphyria, and (3) understanding hepatic failure in protoporphyria.

UI	MeSH Term	Description	Entries
D008107	Liver Diseases	Pathological processes of the LIVER.	Liver Dysfunction,Disease, Liver,Diseases, Liver,Dysfunction, Liver,Dysfunctions, Liver,Liver Disease,Liver Dysfunctions
D010787	Photosensitivity Disorders	Abnormal responses to sunlight or artificial light due to extreme reactivity of light-absorbing molecules in tissues. It refers almost exclusively to skin photosensitivity, including sunburn, reactions due to repeated prolonged exposure in the absence of photosensitizing factors, and reactions requiring photosensitizing factors such as photosensitizing agents and certain diseases. With restricted reference to skin tissue, it does not include photosensitivity of the eye to light, as in photophobia or photosensitive epilepsy.	Actinic Reticuloid Syndrome,Dermatitis, Actinic,Photodermatitis,Chronic Actinic Dermatitis,Photosensitization,Actinic Dermatitides,Actinic Dermatitides, Chronic,Actinic Dermatitis,Actinic Dermatitis, Chronic,Actinic Reticuloid Syndromes,Chronic Actinic Dermatitides,Dermatitides, Actinic,Dermatitides, Chronic Actinic,Dermatitis, Chronic Actinic,Disorder, Photosensitivity,Disorders, Photosensitivity,Photodermatitides,Photosensitivity Disorder,Reticuloid Syndrome, Actinic,Reticuloid Syndromes, Actinic,Syndrome, Actinic Reticuloid,Syndromes, Actinic Reticuloid
D011524	Protoporphyrins	Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D005294	Ferrochelatase	A mitochondrial enzyme found in a wide variety of cells and tissues. It is the final enzyme in the 8-enzyme biosynthetic pathway of HEME. Ferrochelatase catalyzes ferrous insertion into protoporphyrin IX to form protoheme or heme. Deficiency in this enzyme results in ERYTHROPOIETIC PROTOPORPHYRIA.	Heme Synthetase,Porphyrin-Metal Chelatase,Protoheme Ferro-Lyase,Zinc Chelatase,Chelatase, Porphyrin-Metal,Chelatase, Zinc,Ferro-Lyase, Protoheme,Porphyrin Metal Chelatase,Protoheme Ferro Lyase,Synthetase, Heme
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D046351	Protoporphyria, Erythropoietic	An autosomal dominant porphyria that is due to a deficiency of FERROCHELATASE (heme synthetase) in both the LIVER and the BONE MARROW, the last enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features include mainly neurological symptoms, rarely cutaneous lesions, and elevated levels of protoporphyrin and COPROPORPHYRINS in the feces.	Erythropoietic Protoporphyria,Erythrohepatic Protoporphyria,Ferrochelatase Deficiency,Heme Synthetase Deficiency,Deficiencies, Ferrochelatase,Deficiencies, Heme Synthetase,Deficiency, Ferrochelatase,Deficiency, Heme Synthetase,Erythropoietic Protoporphyrias,Ferrochelatase Deficiencies,Heme Synthetase Deficiencies,Protoporphyrias, Erythropoietic,Synthetase Deficiencies, Heme,Synthetase Deficiency, Heme