Final diagnosis: Erythropoietic porphyria with decompensated cirrhosis

Discussion: The term “porphyria” is derived from the Greek word “porphyra,” which means “purple. Erythropoietic protoporphyria (EPP) was first comprehensively described in 1961. Since this initial description, EPP has been reported worldwide.¹ It is now recognized as the most common porphyria in children and the third most common in adults, after porphyria cutanea tarda and acute intermittent porphyria. The incidence is similar in males and females. EPP typically presents in early childhood with painful photosensitivity, although the cause of the photosensitivity that these patients experience is often overlooked until later in life. Hepatobiliary complications include protoporphyrin-containing gallstones and, in less than 5 percent of cases, severe liver failure.² Protoporphyric hepatopathy often presents as an acutely and rapidly progressive form of liver disease with severe right upper quadrant pain, jaundice, nausea, and vomiting. Dramatic elevations of liver function tests are seen. The abdominal pain may be mistakenly attributed to gallstones, which may be present but asymptomatic. Such patients may already have underlying chronic liver disease.³ The latter rare complication is what happened with this gentleman as he had progressive deterioration of liver function that was complicated by lung and kidney failure.  

EPP is inherited in an autosomal recessive and/or autosomal codominant manner depending on the enzyme gene mutation involved^2,4 In about 96% of cases, an affected individual inherits a loss-of-function FECH allele (coding for ferrochelatase enzyme involved in heme synthesis) from one parent and a low-expression FECH allele from the other parent.4 In about 4% of cases, an affected individual has two loss-of-function FECH alleles. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) and individuals who inherit two low-expression alleles are asymptomatic. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.⁴ This particular patient had the mutation associated with marked depletion of ferrochelatase activity; however, he did not have a gene duplication or deletion in addition to this mutation. His sister who is currently still living has a worse phenotype. There is known linkage disequilibrium and phenotypic variation in heterozygotes.⁴

Endnotes