Protoporphyria in Adult
X-linked protoporphyria (XLP) is caused by a gain-of-function mutation in the 5-aminolevulinate synthase (ALAS2) gene. ALAS2 catalyzes the formation of 5-aminolevulinate (ALA) from glycine and succinyl coenzyme A in erythrocytes.
In both, protoporphyrins build up in erythrocytes, bone marrow, skin, and liver. In the presence of visible light in the Soret band (400-410 nm) and oxygen, protoporphyrins release energy, and the resultant reactive oxygen species damage tissues. Erythrocyte protoporphyrin levels have been positively correlated with disease severity.
EPP and XLP is seen in all populations but is rare in people of African descent. Males and females are equally affected.
EPP and XLP present with similar clinical findings; XLP may have more severe manifestations. The hallmark is painful photosensitivity after brief exposures to sunlight. Symptoms are therefore worse in spring and summer and may begin in infancy or early childhood. Itch or discomfort is experienced in sun-exposed skin after minutes to hours and progresses to pain with more prolonged exposure. Pain may last for hours up to a week and may be severe and incapacitating. Babies with EPP may cry on exposure to sunlight, and older children and adults may become sun avoidant, which can affect overall quality of life.
Edema and sometimes purpura of sun-exposed skin may be the only acute physical finding. Redness and petechiae may be seen. Vesicles and crusted erosions occur infrequently. Signs of chronicity include superficial scars on nose and cheeks and radial scars around the mouth. The skin may appear thickened over the central face and small joints of the dorsal hands.
Hypochromic microcytic anemia may occur. Vitamin D deficiency may be secondary to sun avoidance. A minority of patients as adults develop cholestatic hepatitis that may progress to liver failure.
For more information on XLP, see OMIM.
E80.0 – Hereditary erythropoietic porphyria
51022005 – Erythropoietic protoporphyria
Phototoxic drug eruptions – Shorten the time it takes for sunburn to occur. Culprit drugs include doxycycline and non-steroidal anti-inflammatory drugs (NSAIDs).
Polymorphous light eruption – Itch, not pain, and papulovesicles predominate.
Solar urticaria – Itchy wheals occur within minutes of exposure to sunlight.
- Congenital erythropoietic porphyria (CEP; Gunther disease) – Onset is usually at birth, during infancy, or in childhood. Clinical manifestations are more severe with bulla formation and friable skin in sun-exposed areas. Scarring and secondary infection lead to bone resorption (photomutilation). Reddish brown discoloration of teeth (erythrodontia) and hypertrichosis are also seen.
- Hepatoerythropoietic porphyria – Clinical manifestations are similar to CEP.