/X-linked erythropoietic protoporphyria

X-linked erythropoietic protoporphyria

Rare Disease

MONDO:0010420

Also Known As

ALAS2-related erythropoietic protoporphyriaX-linked dominant erythropoietic protoporphyriaX-linked dominant protoporphyriaXLDPPXLPPerythropoietic protoporphyria, X-linkedErythrohepatic protoporphyria, X-linkedXLEPPXLPprotoporphyria, erythropoietic, X-linkedprotoporphyria, erythropoietic, X-linked dominant

Definition

An erythropoietic protoporphyria in which the cause of the disease is a hemizygous, heterozygous, or homozygous (rare) gain-of-function (GOF) variant (X-linked inheritance pattern) in the terminal regulatory exon of ALAS2. GOF variants increase ALAS2 activity resulting in pathway upregulation and high levels of protoporphyrin IX (PPIX). Males with hemizygous variants frequently present in early childhood with severe cutaneous photosensitivity and laboratory markers of liver disease. Heterozygous females can present with symptoms ranging from as severe as affected males to asymptomatic due to random X-chromosome inactivation. This disease is clinically indistinguishable from FECH-related erythropoietic protoporphyria.