The porphyrias are a group of inherited disorders resulting from enzyme defects in the heme biosynthetic pathway. Depending on the specific enzyme involved, various porphyrins and their precursors accumulate in different specimen types. The patterns of porphyrin accumulation in erythrocytes and plasma and excretion of the heme precursors in urine and feces allow for the detection and differentiation of the porphyrias.
Testing protoporphyrin fractions is most informative for patients with a clinical suspicion of erythropoietic protoporphyria (EPP) or X-linked dominant protoporphyria (XLDPP). Clinical presentation of EPP and XLDPP is identical with onset of symptoms typically occurring in childhood. Cutaneous photosensitivity in sun-exposed areas of the skin generally worsens in the spring and summer months. Common symptoms may include itching, edema, erythema, stinging or burning sensations, and occasionally scarring of the skin in sun-exposed areas. Although genetic in nature, environmental factors exacerbate symptoms, significantly impacting the severity and course of disease.
EPP is caused by diminished ferrochelatase resulting in significantly increased free protoporphyrin levels in erythrocytes, plasma, and feces.
XLDPP is caused by gain-of-function variants in the C-terminal end of ALAS2 gene and results in elevated erythrocyte levels of free and zinc-complexed protoporphyrin in erythrocytes, and total protoporphyrin levels in plasma and feces.
Other possible causes of elevated erythrocyte zinc-complexed protoporphyrin may include:
-Iron-deficiency anemia, the most common cause
-Chronic intoxication by heavy metals (primarily lead) or various organic chemicals
-Congenital erythropoietic porphyria (CEP), a rare autosomal recessive porphyria caused by deficient uroporphyrinogen III synthase
-Hepatoerythropoietic porphyria (HEP), a rare autosomal recessive porphyria caused by deficient uroporphyrinogen decarboxylase