Porphyrias
An umbrella term, porphyrias are metabolic disorders that affect the biosynthesis of heme (a component of hemoglobin) and cause excessive production and excretion of porphyrins or their precursors. Porphyrins, which are present in all protoplasm, play a role in energy storage and use. The classification of porphyrias depends on the site of excessive porphyrin production: They may be erythropoietic (erythroid cells in bone marrow), hepatic (in the liver), or erythrohepatic (in bone marrow and in the liver).
Causes
Porphyrias are inherited as autosomal dominant traits, except for Günther’s disease (an autosomal recessive trait) and toxic-acquired porphyria (usually a result of lead ingestion or lead exposure). Enzymatic defects occurring in the heme synthetic pathway cause porphyrias.
Complications
Hepatic porphyrias may result in neurologic and hepatic dysfunction. Acute intermittent porphyria may result in flaccid paralysis, respiratory paralysis, and death. Erythropoietic porphyrias may cause hemolytic anemia.
Assessment
Clinical findings vary widely, depending on the clinical variant of porphyria. (See Types of porphyria, pages 732 and 733.)
A patient with hepatic porphyria may complain of mild or severe abdominal pain, possibly accompanied by nausea, vomiting, and constipation. Many patients with porphyrias also report photosensitivity. The patient history may help pinpoint precipitating factors, such as the use of certain medications, hormonal changes during the menstrual and premenstrual cycles, infection, and malnutrition.
Neurologic examination may reveal paresthesia, hypoesthesia, neuritic pain, psychosis, and seizures.
Depending on the type of porphyria, inspection findings may include skin lesions (possibly associated with erythema, altered pigmentation, and edema in areas exposed to light); changes in urine color; and neurologic signs, such as wristdrop and footdrop. If hemolytic anemia occurs, expect to find splenomegaly on palpation.
In a patient with acute intermittent porphyria, auscultation may reveal wheezing and dyspnea, compounded by the patient’s anxiety. During an acute attack, fever may occur.
Diagnostic tests
In acute intermittent porphyria, the Watson-Schwartz test may be positive for porphobilinogen in the urine; the ion exchange chromatography test may identify aminolevulinic acid in the urine.
In variegate porphyria, protoporphyrin and coproporphyrin may be positive in the stools. With hereditary coproporphyria, large amounts of coproporphyrin appear in the stools and, to a lesser extent, in the urine.
Porphyria cutanea tarda results in increased excretion of uroporphyrins; the amount of fecal porphyrins varies.
With Günther’s disease, porphyrins are found in the urine, especially uroporphyrin I.
With erythropoietic protoporphyria, fluorescent microscopy is used to confirm the diagnosis by detecting excess protoporphyrin in the red blood cells.
A urine lead level of 0.2 mg/L helps confirm toxic-acquired porphyria.
Types of porphyria
| |||||||||||
