Obstacles to Early Diagnosis of Acute Hepatic Porphyria: Current Perspectives on Improving Early Diagnosis and Clinical Management

Abstract

Porphyrias are, for the most part, inherited disorders of the heme biosynthetic pathway which lead to accumulation of specific intermediates responsible for most of the symptoms and signs of biochemically active disease. Acute hepatic porphyrias usually come to clinical attention primarily in women in their reproductive years who present with episodic, severe, generalized abdominal pain. Such acute attacks may also be associated with tachycardia, systemic arterial hypertension, hyponatremia, recent history of dark reddish to brownish urine, and anxiety, delirium, and sensory or motor neuropathies. Diagnosing AHPs is often challenging, requiring a high index of suspicion and the appropriate testing showing elevated ALA and/or PBG in a random urine specimen. Obstacles to diagnosis include inappropriate testing for porphyrins only, inadequate sample handling, and ordering genetic testing as the initial diagnostic test. While some of these pitfalls in diagnosis are surmountable with current knowledge, others are in need of more research.

Keywords: ALA; PBG; acute intermittent porphyria; diagnosis; misdiagnosis; obstacle to diagnosis; porphyria; porphyrins; secondary coproporphyrinuria.

Figure 1

The pathway of heme synthesis, showing pathway intermediates and end-product regulation by heme. The eight steps of heme synthesis (left columns) are shown with the enzyme (middle column) that catalyzes each step. The enzymes in bold face are the clinically most prevalent porphyrias. Acute intermittent porphyria is the most common acute hepatic porphyria.