Literature
Clinical Pearls & Morning Reports
Published December 15, 2021
What laboratory finding distinguishes acute intermittent porphyria from lead poisoning?
Lead poisoning should be considered in any patient presenting with signs and symptoms of porphyria. It mimics the clinical presentation of acute intermittent porphyria with abnormal urinary porphyrin levels. Read the NEJM Case Records of the Massachusetts General Hospital here.
Clinical Pearls
Q: What causes the clinical features of porphyria?
A: Porphyria refers to a group of metabolic disorders that involve the heme biosynthetic pathway. Eighty percent of heme is produced in the bone marrow, where it combines with globin to form erythroid cells. The remainder of heme is produced in the liver and in cells outside the liver to make cytochrome P450 enzymes and other proteins. Heme synthesis begins in the mitochondria with succinyl–coenzyme A and glycine. It involves eight steps, each with a unique enzyme that advances the precursor products along the pathway. The enzyme that initiates the synthesis pathway, delta-aminolevulinic acid synthase (ALAS), differs in the liver (ALAS1) and bone marrow (ALAS2), as does the regulatory feedback control. Disruptions in the pathway resulting from enzyme deficiencies cause precursors to accumulate. The accumulation of porphyrin precursors (delta-aminolevulinic acid [ALA] or porphobilinogen [PBG]) or porphyrins (i.e., uroporphyrin, coproporphyrin, or protoporphyrin) leads to the clinical features of porphyria.
Q: Describe the classic presentation of acute intermittent porphyria.
A: Acute intermittent porphyria is caused by a partial deficiency in the third enzyme of heme synthesis, PBG deaminase. Acute intermittent porphyria is an autosomal dominant disorder, although it has a low penetrance; less than 10% of persons with a pathogenic mutation have symptoms. The classic presentation of acute intermittent porphyria occurs in young women, with symptoms of fatigue, difficulty concentrating, abdominal pain, nausea, and vomiting. Common laboratory findings in patients with acute intermittent porphyria include hyponatremia and mild elevations in liver-enzyme levels.
Morning Report Questions
Q: What laboratory finding distinguishes acute intermittent porphyria from lead poisoning?
A: During attacks of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, the urinary PBG level is expected to be elevated, at 20 to 300 mg per gram of creatinine, accompanied by elevations in the levels of ALA and total urinary porphyrin. An elevation in the ALA level but not the PBG level suggests ALA dehydratase deficiency, which is associated with ALA dehydratase–deficiency porphyria (an extremely rare disease), lead poisoning, and hereditary tyrosinemia. ALA dehydratase inhibition can fully explain the elevations in the levels of urinary ALA, coproporphyrin, and erythrocyte zinc protoporphyrin that are seen in persons with lead poisoning.
Q: How do blood lead levels correlate with symptoms and the need for chelation therapy?
A: Lead poisoning causes a range of nonspecific symptoms, depending on the blood lead level. Adults with blood lead levels between 30 and 50 μg per deciliter can have mild symptoms, including fatigue, irritability, and headache. More severe symptoms are seen with high lead levels (>70 μg per deciliter) and can include anemia, constipation, colicky abdominal pain, and peripheral neuropathy; if the level is higher than 100 μg per deciliter, cerebral edema, encephalopathy, coma, or death can occur. The primary strategy for the management of lead poisoning is removal of the source of exposure. Chelation therapy is recommended for all adult patients with a blood lead level of 100 μg per deciliter or higher, for most adult patients with a blood lead level of 80 μg per deciliter or higher, and for some adult patients with symptoms of lead poisoning and a blood lead level of 50 μg per deciliter or higher.