Prevalence and clinical features of acute intermittent porphyria: a retrospective analysis.

Abstract

To the Editor: Acute intermittent porphyria (AIC) is a rare inherited entity characterized by abdominal pain and a wide range of nonspecific symptoms that can be exacerbated through a multitude of environmental factors.1 Public attention has been given to the acute porphyrias because they may have affected the character of King George III and the creative genius of Vincent van Gogh.2 The porphyrias are eight genetically distinct metabolic disorders, mainly inherited, in which there are defects in normal porphyrin and heme synthesis. Traditionally, the porphyrias have been classified as hepatic or erythropoietic, although some have overlapping features.3 The cardinal clinical features are cutaneous (due to the skin-damaging effects of excess deposited porphyrins) or neurovisceral attacks of pain, sometimes with weakness, delirium, and seizures. Of the acute hepatic porphyrias, the most frequent is autosomal-dominant AIC—a metabolic disorder of heme synthesis due to a deficiency in the porphobilinogen deaminase enzyme; it affects women more than men and has a low penetrance, which is one reason why different clinical manifestations appear at different ages; moreover, because the wide range of nonspecific symptoms may occur with more-common conditions, individuals with AIP may not be readily diagnosed.3 There is an ethnic predisposition in Northern European countries known as Swedish porphyria.1 The purpose of this study was to document the prevalence and clinical features of AIC in a department of internal medicine. Between January 2006 and December 2013, 7,895 hospitalized individuals on a medical ward were retrospectively evaluated; four (0.05%) with AIC were identified (three female, one male, aged 85, 75, 90, and 81); the remaining individual with other types of porphyria are not included in this analysis. All individuals were hospitalized for recurrent acute abdominal pain, vomiting, weakness, and confusion. Patient 2 also had orthostatic hypotension and bradycardia. Factors precipitating the acute attack were severe weight loss due to stomach cancer in Patient 3, urinary tract sepsis in Patients 1 and 2, and alcohol abuse in Patient 4. Physical examination found no abnormalities in any of these individuals except for moderate quadriparesis in Patient 3 and abnormal behavior with hallucinations. Cerebral magnetic resonance imaging, abdominal computed tomography, gastroscopy, and colonoscopy were all normal. Electromyography showed acute motor neuropathy in Patient 3, and cerebrospinal fluid test revealed slightly high protein levels in all four. Patient 3 had low serum sodium level (124 mmol/L). When a urinary catheter was placed, dark urine (Figure 1) was drained; urinalysis showed no hematuria or pyuria.4 A diagnosis of AIP was confirmed in all four individuals because of high urinary excretion of porphobilinogen. They were treated with hematin and adequate calorie intake, and symptoms resolved in all in 2 to 3 days. There were no serious complications or mortality in this series, confirming a good prognosis for individuals with AIP who receive appropriate treatment. Its prevalence is estimated to be from 5 to 10 in 100,000;1 the current study indicates that this is an underestimation because of misdiagnosis and long periods of latency. Clinical manifestations are ambiguous; AIC is called “little imitator,” with symptoms of abdominal pain, peripheral neuropathy, orthostatic hypotension, hyponatremia, and mental disturbances; and abdominal pain, the most common symptom, is usually acute, severe, steady, and poorly localized. Drugs, alcohol, fasting, stress, and infection are the most common precipitants of acute attacks. The important part of management is to suspect and confirm the diagnosis as early as possible in order to treat the attack and avoid inappropriate treatments that may exacerbate the crisis.1 Altered urine color (red or brownish) in the presence of inexplicable acute abdominal pain might suggest the diagnosis, which can be confirmed according to high porphobilinogen concentration in fresh urine protected from light.3 In particular, in elderly adults, abdominal pain and delirium are frequently present, so AIC should be suspected in the presence of unexplained abdominal pain or other characteristic symptoms and signs. Once the diagnosis is confirmed, it is important to remove all potential precipitating factors. In particular, all medication must be checked for safety; the Welsh Medicines Information Centre (www.wmic.wales.nhs.uk/porphyria_info.php) and the Norwegian Porphyria Centre (www.drugs-porphyria.org) offer a specialist advisory service on the safe use of drugs in porphyria.5 Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors had a role in study concept and design, acquisition of subjects, analysis and interpretation of data, and preparation of manuscript. Sponsor's Role: None.