American Journal of Critical Care. 2009;18: 180-178 doi:10.4037/ajcc2009196
Copyright © 2009 by the American Association of Critical-Care Nurses.
Cases of Note features peer-reviewed case reports and case series that document clinically relevant findings from critical and high acuity care environments. Cases that illuminate a clinical diagnosis or a management issue in the treatment of critically and acutely ill patients and include discussion of the patient’s experience with the illness or intervention are encouraged. Proposals for future Cases of Note articles may be e-mailed to ajcc{at}aacn.org.
Acute Intermittent Porphyria as a Cause of Respiratory Failure: Case Report
By
Folkert W. Asselbergs, MD, PhD,
Ton K. Kremer Hovinga, MD, PhD,
Cees Bouwsma, MD and
Jan van Ingen, MD, PhD.
Folkert W. Asselbergsis a fellow in the Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands. Ton K. Kremer Hovingais a nephrologist in the Department of Internal Medicine, Cees Bouwsmais a neurologist in the Department of Neurology, and Jan van Ingenis an intensivist in the Department of Intensive Care Medicine, Martini Hospital, Groningen, the Netherlands.
Corresponding author: Folkert W. Asselbergs, Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands (e-mail: fwasselbergs{at}hotmail.com).
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Abstract
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A 45-year-old man with end-stage renal disease due to polycystic kidney disease was admitted to the hospital because of recurrent abdominal pain, progressive peripheral motor neuron neuropathy, and respiratory failure. The diagnosis of acute intermittent porphyria was confirmed by an elevated porphyrin concentration in the urine and the presence of an R167Q mutation in the porphobilinogen deaminase gene. Use of hydroxyzine, weight loss, and/or a mild upper respiratory viral infection might have been the provoking factor of the acute intermittent porphyria. Treatment with intravenous hemin (3 mg/kg) and a high-carbohydrate diet (3000 kcal/d) had no clinical effect. Tetraplegia and chronic respiratory insufficiency developed, and the patient needed a pacemaker because of a symptomatic sinus bradycardia due to autonomic dysfunction. The patient died 10 months after the first manifestation of acute intermittent porphyria.
Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by a deficiency of porphobilinogen (PBG) deaminase, which is involved in heme biosynthesis. As compensation for the diminished PBG activity, activity of aminolevulinate dehydratase, which is under control of negative feedback from heme, is increased.
Patients with AIP have acute episodes of neurovisceral problems accompanied by increased excretion of porphyrin precursors.1 The first clinical manifestations of AIP are often acute abdominal pain (estimated incidence, 85%–95%) and peripheral neuropathy with muscle weakness (42%–68%).2 Less common and less well-known is respiratory failure (9%–20%).2 The exact underlying mechanisms of these signs and symptoms are unknown. The prevalence of symptomatic AIP is 2 to 3 cases per 100 000 per year.1
AIP can be provoked by inadequate nutrition, infection, alcohol, chemicals, stress, smoking, estrogen, and drugs. Certain drugs can exacerbate AIP by inducing the hepatic hemoprotein cytochrome P450, a situation that leads to a depletion of the free heme pool, resulting in induction of aminolevulinate dehydratase. A list of safe and unsafe drugs for patients with porphyria is available.3 Treatment of AIP consists of 3 elements: eliminating all precipitating factors by discontinuing drugs or treating infections, starting a high-carbohydrate diet or glucose infusion, and starting a hemin infusion.1,2
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Case Report
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A 45-year-old man was admitted to the hospital because of recurrent diffuse abdominal pain, predominantly in the right flank. He had been admitted twice before because of abdominal pain and hematuria, which were attributed to bleeding of a renal cyst for which acetaminophen (paracetamol) and tramadol were prescribed. The patient had end-stage renal disease with a residual diuresis of 1200 mL/24 h due to polycystic kidney disease. He underwent chronic intermittent hemodialysis 3 times a week. He was using the following drugs at the time of admission: hydroxyzine 25 mg 4 times per day, temazepam 10 mg 4 times per day, enalapril 5 mg 4 times per day, sevelamer 800 mg 3 times per day, multivitamins, epoetin beta 2000 units once per week, iron sucrose injection 100 mg once per week, and nadroparin 2850 units during dialysis. Some weeks before admission, the patient had a weight loss of about 7 kg that was preceded by a mild upper respiratory viral infection. Furthermore, paresis of the extensors of the right wrist and the left fingers developed. The sensibility and reflexes of the arms were normal. During the course of several weeks, areflexia and peripheral motor neuron paralysis developed in both arms, a pattern that is not typical for Guillain-Barré syndrome.
| The patient had acute abdominal pain, loss of extremity motor strength, and respiratory failure.
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Analysis of fluid obtained by lumbar puncture showed no elevation of total protein, and an electromyogram showed no signs of demyelinization. During the electromyogram, the patient spontaneously reported that his mother had symptomatic AIP. His next of kin were tested for AIP once, but the patient was not. Laboratory tests ordered because of this new information clearly showed elevations in urinary porphyrin, 
-aminolevulinic acid, and PBG (see Table
), and genotyping revealed the R167Q mutation in the PBG deaminase gene (chromosomal region 11q24.1–11q24.2). In retrospect, several factors may have triggered the AIP. Hydroxyzine use, weight loss, and/or the mild upper respiratory viral infection could have been the provoking factor.
At admission, intravenous hemin (3 mg/kg) was administered. The motor paralysis, however, progressed to the respiratory muscles, and respiratory insufficiency developed. The patient was admitted to the intensive care unit for intubation and mechanical ventilation. Arterial blood gas analysis showed severe hypoxemia: pH 7.48, PaCO2 5.5 kPa (to convert kilopascals to millimeters of mercury, divide by 0.133), PaO2 6.9 kPa, bicarbonate 31 mmol/L, base excess 6.7 mmol/L, and arterial oxygen saturation 91.7%.
In the intensive care unit, a high-carbohydrate diet (3000 kcal/d) was started, and the hemin infusions were continued for a total of 6 days. The urine porphyrin and ALA levels decreased, but the urine PBG levels remained elevated after treatment with hemin. Interestingly, porphyrin, PBG, and -aminolevulinic acid were all present in dialysis fluid (uroporphyrin 5.1 nmol/L, PBG 1.5 nmol/L, and -aminolevulinic acid 2.3 nmol/L). After intubation, thoracic negative pressure was –2 cm H2O initially, –10 cm H2O after 5 days, and –30 cm H2O after 8 days; a successful extubation was performed on day 8. The peripheral motoric polyneuropathy progressed, and except for the abductors of both legs, no motor strength was present in the extremities. In addition, the patient had noninvasive ventilatory support for respiratory failure, and a pacemaker was implanted to treat a symptomatic sinus bradycardia due to autonomic dysfunction. Additional hemin infusions had no detectable clinical effect, and a liver transplant was not feasible because of the patient’s condition.
Because of the progressive nature, the irreversibility, and the fatal prognosis of the disease, the patient’s team of physicians, together with the patient himself, decided he should have no resuscitation and no intubation the next time an episode of AIP occurred. The patient was transferred to a nursing home and died a week later with signs and symptoms of AIP triggered by a recurrent respiratory infection.
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Conclusion
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AIP is a rare but fatal disease and should be considered in patients with acute abdominal pain, polyneuropathy, and respiratory failure. Future research is needed to investigate new treatment options and to define clinical parameters to monitor treatment effects and outcome in patients with AIP.
FINANCIAL DISCLOSURES
None reported.
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REFERENCES
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- Herrick AL, McColl KE. Acute intermittent porphyria. Best Pract Res Clin Gastroenterol. 2005;19(2):235–249.[CrossRef][Medline]
- Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias [published correction appears in Ann Intern Med. 2005;143(4):316]. Ann Intern Med. 2005;142(6):439–450.[Abstract/Free Full Text]
- The drug database for acute porphyria. Database developed by the Norwegian Porphyria Centre (NAPOS). http://www.drugs-porphyria.org. Accessed December 27, 2008.
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