Even though AIP is the most common type of acute hepatic porphyria the estimated prevalence of the disease in Europe countries is 5.4 in per million [5]. There is no data available regarding the prevalence of the disease in Sri Lanka. Review of literature did not disclose any previous Sri Lankan case reports of a genetically confirmed patient with AIP. Since porphyrias are uncommon the clinicians rarely acquire familiarity with these disorders and the curriculum of medical schools focuses very little on these disorders.
Watson and Schwartz test is a screening test for urine PBG. 2 mL of urine is mixed with equal amount of Ehrlichs reagent. If PBG is present it will form porphobilinogen- Ehrlich complex, a red chromogen which is characteristically insoluble in chloroform and N-butanol. When chloroform is added PBG extracts into and gives a red color to the upper aqueous layer, whereas urobilinogen-Ehrlich complex extracts into the chloroform layer. Since patients in acute attacks excrete large amounts PBG false negative results are rare during an acute attack. Spectrophotometry of acidified urine is a semi-quantitative method which can be used as a screening test, to detect urine total porphyrin levels. All porphyrins display an absorption band near 400 nm. In a setting like Sri Lanka, even though sophisticated methods are not widely available these simple reliable laboratory tests are very useful to initiate a diagnosis of a porphyria [6, 7]. To date, quantitative tests for PBG, ALA, uroporphyrin and coproporphyrin levels and genetic studies for porphyria are not available in Sri Lanka. Definitive diagnosis of porphyria should be carried out in an overseas laboratory. Molecular diagnostic studies are useful not only to confirm a biochemically proven AIP but also to identify at risk family members [8].
It is estimated that the penetrance of acute attacks is approximately 1% in heterozygotes with likely HMBS pathogenic variants [9]. R173W mutation has been previously reported worldwide, from Sweden, Russia, Spain, United Kingdom, Japan and China. Compared to other common mutations R173W mutation is likely to have a higher clinical penetrance and increased seriousness. This missense mutation is a C-T substitution in nucleotide 517 in exon 10. Conversion of arginine to tryptophan in the mutant protein results in reduced enzyme activity. Even though erythrocyte PBGD activity can be used as an indicator of disease severity the levels can be normal in some patients having acute attacks [10,11,12,13,14,15,16].
The most effective treatment in managing acute attacks is intravenous haem arginate, which is available in Europe and many other countries worldwide but not in Sri Lanka. The precipitating factors should be removed. Carbohydrate loading alone may be helpful in mild attacks. While administering the treatment the urinary excretion of ALA and PBG has to be monitored to assess the response. Supportive management includes narcotic analgesics, antiemetics, anxiolytics, correction of dehydration, monitoring fluid balance and psychological support. Strategies in controlling recurrent acute attacks include avoidance of potential trigger factors and prophylactic hemin infusion [17, 18]. However, this patient encounters the disadvantages such as lack of therapeutic and prophylactic heam arginate and lack of monitoring for response to such treatment with quantitative measurement of ALA and PBG due to unavailability and prohibitive cost of such facilities. Therefore long standing resolution of symptoms in this patient is not feasible.
Patients with acute intermittent porphyria usually present with acute attacks with neurovisceral manifestations which are common to several medical, psychiatric and surgical pathologies. Thus, patients with a porphyria, including the acute porphyrias, can potentially encounter the problem of underdiagnosis and misdiagnosis, severely extending the time between onset of symptoms and confirmed diagnosis, resulting in mismanagement and potentially severe debilitating irreversible effects and even death. Medical misdiagnoses can lead to complications in acute porphyria patients due to the possible prescription of porphyrogenic drugs [19]. Surgical misdiagnoses lead to unnecessary surgical interventions like appendectomy and diagnostic laparoscopy. There have been case reports of AIP presenting with psychosis as the only clinical manifestation as well [20]. Under diagnosis of AIP in this category may have complications in patients due to some antipsychotics which could significantly worsen the symptoms of a patient with an acute porphyria. Therefore, a high index of suspicion and awareness of front line laboratory investigations is important for appropriate diagnosis. Definitive diagnosis of a patient with AIP enables implementation of strategies to prevent acute attacks, and also triggers screening and genetic counseling of at-risk family members.