Abstract
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. The ubiquitous FECH catalyzes the insertion of iron into the protoporphyrin ring to generate the final product, heme. After hemoglobinization, FECH can utilize other metals like zinc to bind the remainder of the protoporphyrin molecules, leading to the formation of zinc protoporphyrin. Therefore, FECH deficiency in EPP limits the formation of both heme and zinc protoporphyrin molecules. The erythroid-specific ALAS2 catalyses the synthesis of delta-aminolevulinic acid (ALA), from the union of glycine and succinyl-coenzyme A, in the first step of the pathway in the erythron. In XLP, ALAS2 activity increases, resulting in the amplified formation of ALA, and iron becomes the rate-limiting factor for heme synthesis in the erythroid tissue. Both EPP and XLP lead to the systemic accumulation of protoporphyrin IX (PPIX) in blood, erythrocytes, and tissues causing the major symptom of cutaneous photosensitivity and several other less recognized signs that need to be considered. Although significant advances have been made in our understanding of EPP and XLP in recent years, a complete understanding of the factors governing the variability in clinical expression and the severity (progression) of the disease remains elusive. The present review provides an overview of both well-established facts and the latest findings regarding these rare diseases.
Highlights
Protoporphyria (PP) is a rare genetic metabolic disorder caused by inborn defects in enzymes of the heme-biosynthetic pathway
A lack of vitamin D leads to osteoporosis, and to investigate further this condition, a bone mineral density (BMD) test was performed with four males and six females
erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are known as rare photodermatoses resulting in acute, painful, and nonblistering phototoxicity on sun exposure
Summary
Protoporphyria (PP) is a rare genetic metabolic disorder caused by inborn defects in enzymes of the heme-biosynthetic pathway. EPP is an autosomal recessive condition [4] that occurs because of a loss-of-function mutation in one allele of the FECH gene, which is mostly accompanied by a low expression FECH genetic variant (c.315–48C) in the other allele, leading to a 70% decrease in the enzyme activity [5]. Patients can inherit bi-allelic loss-of-function mutations in the FECH gene, which leads to a more severe form of the disease and accounts for about 4% of the cases in Europe. In these patients, the majority of the mutations are missense and inherited in compound heterozygosity [7].
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