The porphyrias

Porphyrias are a group of diseases that result from defective enzymes of heme biosynthesis. The seven different porphyrias correspond to an abnormality of a specific enzyme of the heme biosynthesis pathway. The genes coding for the enzymes are known in all porphyrias, and several mutations have been identified in porphyric patients.

Two major types of clinical manifestations occur in porphyrias. Acute porphyric attack, which is characterized by abdominal pain and neurologic manifestations, is a feature in acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria. In all three conditions the porphyrin precursors porphobilinogen and 5-aminolevulinic acid are accumulated during attacks. In other porphyrias cutaneous symptoms are the principal manifestations.
In symptomatic patients the specific porphyria can easily be diagnosed by specific laboratory tests. Most porphyrias are inherited in autosomal dominant fashion, but the penetrance of the disease varies greatly. In many porphyrias, the majority of patients remain asymptomatic throughout their lives. Biochemical tests are often inaccurate in the diagnosis of latent cases of porphyria. When the underlying mutation in an affected family is known, the DNA diagnosis is accurate, but the genetic heterogeneity of individual porphyrias restricts usefulness of this method.

ACUTE PORPHYRIAS

The acute porphyrias–acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria– are characterized by episodic acute attacks. During an acute attack, symptoms include severe abdominal pain, vomiting, constipation, often pain in the extremities and in the back, and psychologic symptoms that range from anxiety to delirium. Urine may be dark or red in color because of increased amounts of porphobilin and porphyrins. Sometimes the disease progresses to peripheral motor neuropathy with the onset of seizures or cranial nerve palsies. Common clinical findings are hypertension and sinus tachycardia, and routine laboratory findings may include low serum sodium values.

All symptoms during acute attacks are nonspecific, and the diagnosis must be confirmed by appropriate laboratory tests. Laboratory diagnosis is easy, because during attacks all patients, irrespective of the type of porphyria, excrete great amounts of the porphyrin precursors porphobilinogen and 5-aminolevulinic acid. A rapid and relatively reliable qualitative test for porphobilinogen is available. A clearly positive qualitative test is a strong indicator of acute porphyria and allows beginning of therapy. However, the diagnosis must always be confirmed by quantitative tests for porphobilinogen and 5-aminolevulinic acid. During acute attacks the values are usually more than 10 times higher than reference values.

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