|Year : 2014 | Volume
| Issue : 6 | Page : 813-815
Acute Intermitent porphyria and early hematin treatment before confirming the diagnosis
Mustafa Volkan Demir1, Tayfun Temiz2, Selcuk Yaylaci3, Ali Tamer1
1 Department of Internal Medicine, Malatya State Hospital, Malatya, Turkey
2 Department of Internal Medicine, Faculty of Medicine, Sakarya University, Sakarya, Turkey
3 Department of Internal Medicine, Rize Findikli State Hospital, Turkey
|Date of Web Publication||18-Nov-2014|
Mustafa Volkan Demir
Department of Internal Medicine, Malatya State Hospital, Malatya 44100
Source of Support: None, Conflict of Interest: None
The term porphyria refers to a heterogeneous group of metabolic diseases resulting from variable catalytic defects of the enzymes involved in the heme biosynthesis pathway. Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from a partial deficiency of porphobilinogen (PBG) deaminase. A 21-year-old woman presented to us with the complaints of abdominal pain and vomiting. Her father and sister are diagnosed as acute intermittent porfiria. The laboratory findings showed profound hyponatremia, hypokalemia and high values of creatine kinase. AIP was suspected because of family history and clinic of patient. Our initial management consisted of continuous infusion of 10% glucose and 3% NaCI solution. We decided to start hematin treatment because of no clinical response with current therapy. After the hematin treatment she had regained consciousness, the abdominal pain subsided. The hyponatremia and elevation of creatine kinase was corrected. The analysis of PBG in 24-h urine confirmed the diagnosis of AIP.
Keywords: a0 bdominal pain, acute intermittent porphyria, glucose infusion, hematin treatment
|How to cite this article:|
Demir MV, Temiz T, Yaylaci S, Tamer A. Acute Intermitent porphyria and early hematin treatment before confirming the diagnosis. Med J DY Patil Univ 2014;7:813-5
|How to cite this URL:|
Demir MV, Temiz T, Yaylaci S, Tamer A. Acute Intermitent porphyria and early hematin treatment before confirming the diagnosis. Med J DY Patil Univ [serial online] 2014 [cited 2021 Jan 23];7:813-5. Available from: https://www.mjdrdypu.org/text.asp?2014/7/6/813/144898
| Introduction|| |
The term porphyria refers to a heterogeneous group of metabolic diseases resulting from a variable catalytic defect of the enzymes involved in the heme biosynthesis pathway.  Acute intermittent porphyria (AIP) is an autosomal dominant disorder resulting from a partial deficiency of porphobilinogen (PBG) deaminase, the third enzyme in the heme biosynthetic pathway. Symptoms in AIP are due to effects on the visceral, peripheral, autonomic and central nervous systems. They usually occur as intermittent attacks that may be life-threatening. 
Acute porphyria episode can be triggered by environmental factors, reduced calorie intake, medications, alcohol intake, infection, surgery or psychological disorder. Endocrine factors and steroid hormones may also be the cause of attacks.  The most frequent clinical manifestation of acute attacks include vomiting, hypertension and tachycardia, acute abdominal pain (incidence estimated at 85-95%) and peripheral neuropathy with muscle weakness (42-68%). 
Treatment of this condition consists in eliminating the precipitating factors. High-carbohydrate diet, glucose infusion or hematin infusion can also be prescribed.  We report a female patient who presented to us with complaints of abdominal pain, nausea and vomiting and diagnosed as porphyria and treated with hematin infusion before the confirming diagnosis of porphyria.
| Case Report|| |
A 21-year-old woman presented to us with the complaints of abdominal pain and vomiting. Her abdominal pain and nausea started 15 days ago and gradually increased. She used paracetamol 500 mg twice a day. She has no remarkable feature in her medical history. Her father and sister are diagnosed as acute intermittent porfiria. Her consciousness were somnolence. Blood pressure was 158/88 mmHg, pulse 118/min, respirations 22/min, oral temperature 37.1°C and pulse oximetry 97% on room air. Physical examination revealed a healthy, well-nourished young adult with no apparent injury. She was diaphoretic and agitated while guarding her abdomen. There were no motor or sensory deficits. Examination revealed a flat and diffusely tender to light palpation abdomen. Bowel sounds were normal. Chest, cardiac, rectal examinations were unremarkable. Abdominal ultrasonography and direct abdomen graphy was normal. We ruled out acute abdomen with the result of general surgery consultation. The laboratory findings showed profound hyponatremia: 116 mmol/L, hypokalemia: 2.8 mmol/L and high values of creatine phosphokinase (CPK): 15000 IU/L [Table 1]. The urine color was dark and myoglobin was detected in her spot urine analysis. She admitted to our intensive care unit because of electrolyte imbalance and somnolence. AIP was suspected because of family history and clinic of patient. Urine was sent to a special laboratory to show urine PBG. Urine PBG would be reported after 10 days. Initial management consisted of placing a foley catheter and intravenous catheter and continuous infusion of 10% glucose and 3% of NaCI solution. There was no clinical response to this continuous infusion therapy. On admission on the 4 th day, we decided to start hematin treatment because of no clinical response with current therapy and diagnosis of the disease is highly suspected. We infused hematin into the jugular vein with the dose of 4 mg/kg for 3 days. After 6 h from the hematin treatment, she had regained consciousness, the abdominal pain subsided, the blood pressure and heart rate were back to normal. The hyponatremia and elevation of creatine kinase was gradually corrected [Table 1]. The analysis of PBG in 24-h urine confirmed the diagnosis of AIP (PBG: 24.4 mg, reference <1.7 mg). We informed the patient about her disease and drug using in porphyria. We discharged the patient with the suggestion of outpatient control. She presented to the polyclinic with no complaints after 15 days from discharged.
| Discussion|| |
Acute porphyrias usually present with neurovisceral and psychiatric disturbances like abdominal pain, constipation, insomnia, depression, disorientation, and hallucinations. In acute porphyric crisis, encephalopathy varying from confusion to psychosis can occur concomitantly with hypothalamic involvement and metabolic derangement of inappropriate secretions of anti-diuretic hormone (ADH).  Generalized seizures, myoclonic activity or coma may be observed due to neurological effects or hyponatremia.  Our case presented to us with complaints of abdominal pain, nausea, vomiting and somnolence as like as acute abdomen. We rule out acute abdomen. We want to highlight the importance of including AIP in the differential diagnosis of acute abdomen.
Hyponatremia is common in AIP, often due to syndrome of inappropriate ADH.  Hypokalemia is not a common direct consequence of AIP, but may result from vomiting. Her vomiting was sufficiently severe to account for hypokalemia. Hypokalemic metabolic and respiratory alkalosis was detected. Hyperventilation due to anxiety may cause respiratory alkalosis. Our patient also had very high CPK, presumably due to rhabdomyolysis resulting from her hyponatremia and hypokalemia. There was myoglobinuria in her urine biochemical analysis. Both hyponatremia and hypokalemia may contribute to rhabdomyolysis. We think her a-day long vomiting induced hypokalemia could be a reason of rhabdomyolysis.
Autonomic disturbances may manifest as urinary retention, paralytic ileus, restlessness, tremors, excessive sweating, tachycardia and fluctuating blood pressure, typically labile hypertension.  Autonomic dysfunction may be resulting in hypertension and tachycardia as found in our case. Complications like bradycardia and sudden cardiac arrest have also been reported.  There were tachycardia and hypertension in our case.
Prevalence of mutations that lead to AIP is low - 1-2 mutation carriers in 1,00,000 inhabitants, with an exception of the North European countries such as England, Ireland and Sweden, where it reaches the ratio of 1:10.000 inhabitants.  As 80% of mutation carriers are asymptomatic, while in others the disease appears in the form of acute attacks. Genetic analysis was unavailable in our hospital.
Although this condition is very rare in everyday clinical practice and despite the distinct variability of its clinical features, the triad of abdominal pain, tachycardia and neurological and/or psychiatric episodes must point to the diagnosis of AIP, especially in younger women, and in the presence of family history like our case. The urine findings are also characteristic - urine becomes darker after being exposed to sunlight up to dark red or brown color.  Our patient's urine did not become darker after being exposed to sunlight. The analysis of PBG in 24-h urine confirmed our diagnosis of AIP.
Supportive treatment during acute episodes is limited and comprises symptomatic and general supportive measures. Administration of intravenous glucose of up to 400 g/d has been shown to dramatically improve symptoms. It is theorized that glucose exhibits inhibitory effects on porphyrin production similar to heme arginate through the reduction of aminolevulinic acid (ALA) production. Because there is virtually no risk in treatment, glucose should be given to all patients suspected of AIP. , We administrated intravenous glucose with the dose of 400 g/day for 3 days but there was no clinical response.
Hematin (heme arginate) is the only form of heme approved by Food and Drug Administration. Heme reduces porphyrin production through the employment of negative feedback by suppressing ALA synthase, the rate-limiting enzyme within the biosynthetic pathway which normalizes the overproduction and over excretion of ALA and PBG within hours of intravenous administration.  There was no laboratory result that confirms our diagnosis but we decided to start hematin treatment because of her clinic. AIP is a medical emergency and delay in treatment may contribute to serious or even fatal outcomes. We put catheter into the jugular vein for hematin infusion. We infused hematin with the dose of 4 mg/kg for 3 days. After 6 h from the hematin treatment she had regained consciousness, the abdominal pain subsided, the blood pressure and heart rate were back to normal. The hyponatremia and elevation of creatine kinase improved [Table 1]. We advocate that hematin infusion should be started when the diagnosis of AIP is highly suspected before its diagnosis is confirmed. Indeed symptomatic AIP is a medical emergency and delay in treatment may contribute to serious or even fatal outcomes. Hematin infusion should be started empirically without waiting for laboratory confirmation of AIP when the diagnosis of the disease is highly suspected.
AIP should always be included as a differential diagnostic possibility in cases of acute abdominal pain, especially when followed by tachycardia, hypertension and/or neuropsychiatric symptomatology. Family history is very important in the diagnosis. The delayed diagnosis and inadequate therapy can have fatal consequences. If the analysis of PBG in 24-h urine cannot be available or will result later, the clinician should start hematin treatment for AIP. AIP is a medical emergency and delay in treatment may contribute to serious or even fatal outcomes. Hematin infusion should be started empirically without waiting for laboratory confirmation of AIP when the diagnosis of the disease is highly suspected.
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