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X-linked erythropoietic protoporphyria
A rare disorder of heme metabolism characterized by severe cutaneous photosensitivity in affected boys and sometimes in girls, manifesting in childhood.
ORPHA:443197
Classification level: Disorder
- X-linked dominant erythropoietic protoporphyria
- X-linked dominant protoporphyria
- XLDPP
- XLPP
Prevalence: <1 / 1 000 000
Inheritance: X-linked dominant
Age of onset: Childhood
X-linked erythropoietic protoporphyria (XLPP) has been reported with a prevalence <1/1,000,000.
The disease manifests in infancy or childhood through the onset of severe acute cutaneous photosensitivity in affected boys, with tingling, burning and itching within few minutes of exposure to sunlight or illumination in the visible spectrum (in particular, in the Soret band [400 - 410 nm]), often accompanied by skin edema and redness. Pain may persist for several hours or days after the initial reaction. As protoporphyrin is a lipophilic molecule excreted by the liver, some XLPP patients may develop biliary lithiasis and liver damage. In heterozygous girls, the phenotypes vary from asymptomatic to severe.
XLPP is due to gain-of-function mutations in the ALAS2 gene (NM_000032.4) encoding erythrocyte-specific aminolevulinic acid synthase 2.
Diagnosis is based on the presence of high concentrations of protoporphyrin in plasma and red blood cells, and the detection of a plasma fluorescence peak at 635 nm. The percentage of zinc-bound protoporphyrin is reduced but remains higher than in autosomal erythropoietic protoporphyria, and FECH enzyme activity is normal. A liver damage analysis is recommended. Genetic analysis (mutations in the ALAS2 gene) and family screening are also recommended.
Differential diagnosis includes autosomal erythropoietic protoporphyria, phototoxic drug reactions, solar urticaria, contact dermatitis, angioedema, and hydroa vacciniforme.
Antenatal diagnosis is theoretically possible, but not offered.
The transmission pattern is X-linked dominant.
Treatment is based on preventive measures similar to those proposed for the treatment of autosomal erythropoietic protoporphyria. Since liver disease is the major risk in XLPP, regular monitoring of liver function is recommended. Sequential liver and bone marrow transplant should be considered in the treatment of severe cases with liver damage.
The prognosis of XLPP depends on the progression of liver disease. However, photosensitivity can affect patients' quality of life. In contrast to EPP, oral iron supplementation in XLPP patients with iron deficiency anemia reduces the concentration of protoporphyrins in the blood and improves symptoms.
Last update: March 2024 - Expert reviewer(s): Dr Neila TALBI | MetabERN*
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