endocrine and metabolic disorders
Erythropoietic Protoporphyria and X linked Protoporphyria
Etiology
 alleles, or more commonly, one defective and one low-expressing wild-type allele ( Etiology references ). X-linked protoporphyria, which comprises the remaining 10% of cases, results from gain-of-function mutations that increase the activity of erythroid-specific delta-aminolevulinate synthase (ALAS 2) in the bone marrow; inheritance is X-linked. The phenotype of heterozygous females can vary from asymptomatic to that of affected males ( Etiology references ). Prevalence of EPP phenotype is about 1/75,000. However, a study from the UK Biobank found that the prevalence of EPP was about 1/17,000 ( Etiology references ). The authors attributed this higher prevalence to under diagnosis. Protoporphyrin accumulates in bone marrow and red blood cells, enters the plasma, and is deposited in the skin or excreted by the liver into bile. About 10% of patients develop chronic liver disease; a few of these patients develop 1.Balwani M, Doheny D, Bishop DF, et al: Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria.Mol Med19(1):26–35, 2013. doi:10.2119/molmed.2012.00340 2.Dickey AK, Quick C, Ducamp S, et al: Evidence in the UK Biobank for the underdiagnosis of erythropoietic protoporphyria.Genet Med23(1):140–148, 2021. doi:10.1038/s41436-020-00951-8 