The hereditary
porphyrias comprise a group of eight metabolic disorders of the
heme biosynthesis pathway. Each
porphyria is caused by abnormal function at a separate enzymatic step resulting in a specific accumulation of
heme precursors.
Porphyrias are classified as hepatic or erythropoietic, based on the organ system in which
heme precursors (δ-
aminolevulinic acid [ALA],
porphobilinogen and
porphyrins) are overproduced. Clinically,
porphyrias are characterized by acute neurovisceral symptoms, skin lesions or both. However, most if not all the
porphyrias impair hepatic or gastrointestinal function. Acute
hepatic porphyrias present with severe
abdominal pain,
nausea,
constipation,
confusion and seizure, which may be life threatening, and patients are at risk of
hepatocellular carcinoma without
cirrhosis.
Porphyria Cutanea presents with skin fragility and
blisters, and patients are at risk of
hepatocellular carcinoma with liver
iron overload.
Erythropoietic protoporphyria and X-linked protoporphyria present with acute painful photosensitivity, and patients are at risk of
acute liver failure. Altogether,
porphyrias are still underdiagnosed, but once they are suspected, early diagnosis based on measurement of biochemical metabolites that accumulate in the blood, urine, or feces is essential so specific treatment can be started as soon as possible and long-term liver complications are prevented. Screening families to identify presymptomatic carriers is also crucial to prevent overt disease and chronic hepatic complications.