Chapter 10 Heme Biosynthesis and Its Disorders
Porphyrias
Table 10-1 Porphyrias: Clinical Involvement, Enzymatic Etiology, and Chromosomal Location
ALA, 5-Aminolevulinate.
Measurement of Porphyrins and Precursors
Fluorescence of urine under ultraviolet (UV) light is recommended as the initial screening test for the acute porphyrias,1 whereas plasma fluorescent spectroscopy is the best initial test for diagnosis of cutaneous porphyrias.2 Diverse techniques such as high-pressure liquid chromatography,3 quantitative extraction, and various forms of fluorometry are used to measure porphyrins and precursors.4 The International Federation of Clinical Chemistry and Laboratory Medicine presents diagnostic information on the Internet (www.ifcc.org).
Table 10-3 Changes in Porphyrins and Their Precursors in the Porphyrias, Porphyrinurias, and Hereditary Sideroblastic Anemia
ALA, 5-Aminolevulinic acid; PBG, porphobilinogen.
Precipitating Factors in Acute Porphyria
Hormonal status is also important. Attacks are more common in females, and they rarely occur before puberty or after menopause. Pregnancy and oral contraceptives may also precipitate attacks. Some women experience regular attacks, commencing in the week before the onset of menstruation. These may require luteinizing hormone–releasing hormone (LH-RH) antagonists for control (Table 10-4).
Drugs for Porphyria
Before prescribing any medication to a porphyric patient, advice must be sought from an appropriate specialist. Full drug lists are available on the Internet (www.drugs-porphyria.org). It should be borne in mind that such lists are far from encyclopedic, that new drugs are constantly being introduced to the pharmacopoeia, and that any form of combined preparation must be viewed with suspicion, because little is known about metabolic interactions in these diseases.5 More details of such use and side effects of drugs can be sought from the literature.6
Differential Diagnosis of Acute Intermittent Porphyria
Attacks of acute porphyria must be distinguished from other causes of acute abdominal pain or peripheral neuropathy sometimes associated with psychosis.7 Heavy metal poisoning (i.e., lead or arsenic) and Guillain-Barré syndrome must be considered, as well as paroxysmal nocturnal hemoglobinuria with its characteristic early morning hemoglobinuria and abdominal pain.7
A rapid screening test during an acute attack is to mix equal volumes of urine and Ehrlich aldehyde reagent and observe for the pink color of porphobilinogen; alternatively the urine can be left standing in sunlight to observe darkening in color. The differential diagnosis of porphyrias uses qualitative and quantitative measurement of porphyrins and precursors, with subsequent use of enzymatic assay and identification of familial genetic alterations.8
Table 10-4 Precipitating Factors in Acute Porphyria
| Drugs | Other Stimuli |
|---|---|
| Alcohol | Fasting or dieting |
| Barbiturates | Hormones, stress |
| Angiotensin-converting enzyme (ACE) inhibitors | Smoking |
| Anticonvulsants | |
| Antidepressants |
