Acute Intermittent Porphyria- Perplexed by the Purple

Department of Psychiatry, Nepal Police Hospital, Maharjgunj, Kathmandu, Nepal, Department of General Practice and Emergency Medicine, Maharajgunj, Kathmandu, Nepal,Department of Radiology, Nepal Police Hospital, Maharajgunj, Kathmandu, Nepal, 4Department of General surgery, Nepal Police Hospital, Maharajgunj, Kathmandu, Nepal, 5Department of Medicine, Nepal Police Hospital, Maharajgunj, Kathmandu, Nepal, 6Nepal Police Hospital.


INTRODUCTION
The porphyrias are a heterogeneous group of overproduction diseases, resulting from in haem biosynthetic enzymes. 1 Neurological or psychiatric symptoms occur in most acute attacks, and may mimic many other disorders. The diagnosis may be missed because it is not even considered or because of technical problems, such as sample collection and storage, and interpretation of results. 1 The diagnosis of acute porphyrias, however, can be very challenging due to overlapping features amongst the various types.
Here we report a case which caused a similar diagnostic confusion during our assessment and treatment in Nepal Police Hospital. Thorough considerations of multiple differential diagnosis and with evidence from laboratory results and supportive radiological picture, a diagnosis of acute intermittent porphyria was made.

CASE REPORT
Ms X -Sixteen years old unmarried female, studied upto 10th grade, from a low socioeconomic background,a non-smoker and a non-alcoholic presented to the emergency room of Nepal Police Hospital,Kathmandu on 11/7/2074, with chief complaints of pain abdomen since three days and vomiting of same duration.
Abdominal pain was acute on onset, in the epigastric region, colicky in nature, nonradiating, persistent, with waxing and waning intensity. Pain was associated with vomiting which was frequent, non-projectile, nonbilious. Associated with pain and vomiting was constipation of two days duration.
Patient had presented with similar symptoms four months ago, of two weeks duration, along with one episode of unresponsiveness. During that presentation patient was evaluated by the surgical team and provisionally diagnosed as a case of Sub acute intestinal obstruction with hyponatremia, was treated symptomatically over three days of in-patient stay and discharged after symptomatic relief. Unresponsive episode was not paid due attention.
During the current admission due to recurrence of similar symptoms, a thorough investigation was carried out by the surgical team, again with a clinical suspicion of subacute intestinal obstruction, though per Upper Gastro Intestinal (UGI) Endoscopy revealed, mild antral gastritis which did not explain the severity of symptoms. Ultrasonography (USG) abdomen revealed admission revealed dilated bowel loops, otherwise normal. Computed Tomography (CT) scan of abdomen was unremarkable for any abdominal pathology.
During ward stay in the current admission, patient developed an episode of of admission), witnessed by the father and the ward nurse. A detail description of the episode was obtained which characteristically showed sudden unresponsiveness, associated with neck deviation towards the right side with stiffening of the whole body and jerky movements of both upper and lower limbs with a tongue bite on the left lateral part of tongue, lasting for about two to three minutes followed by regaining of consciousness, during which the patient would appear confused for recall the event. This episode was followed by yet another episode of unresponsiveness after 20 minutes with a fully conscious period in between and was similar in pattern as the previous one. Considering both episodes as Complex partial seizure leading to secondary generalization, patient was shifted to intensive care unit for further observation and care. Electro Encephalography (EEG) done in alert and awake state using the international 10-20 system of electrode placement showed alfa as the posterior dominant rhythm with spiky discharges from left temporal and occipital lobe.
During ICU staypersistent hypertension and persistent tachycardiawas observed. The patient didn't have any history of hypertension or any cardiac abnormality. Echocardiography didn't reveal any abnormality.The laboratory investigations were remarkable for persistent hyponatremia.By this time of evaluation thecase was still a diagnostic quagmire-the treating team were not able to come to any conclusive state.
Psychiatry consultation was sought on morbidity could explain the clinical state. Psychiatric evaluation revealed-presence of a stressor in the form of failure in recent exams with features suggestive of panic attacks. But the Psychiatric symptomatology were The clues which hinted towards an "organic" factor lying underneath all this picturewere hyponatremia, persistent tachycardia, persistent hypertension, persistent pain abdomen, persistent vomiting and constipation.This diagnostic confusion lead to search for literaturesand reverting back to textbooks from which a clue to porphyria was found. Further investigations were requested compatible with a case of porphyria. Clinically Irritable bowel syndrome was ruled out. The most common acute porphyria is acute intermittent porphyria (AIP), an autosomal dominant disorder of an enzyme called porphobilinogen (PBG) deaminase. 2 It is an Autosomal Dominant disease.The disease is enzyme (half normal activity), and thus the symptoms of AIP may not appear until the second or third decade of life.Ms X presented with the clinical signs and symptoms at 16 years of age which is at par with usual age of onset of this disorder. Exposure to a precipitating agent can lead to an earlier presentation. 3 Women are more commonly affected than men. 4 The prevalence of acute porphyria among psychiatric patients is 0.21%-0.48% which was considered to be higher than the typical population as mentioned in the article by Tay et al. 5 Acute intermittent porphyria has a prevalence of about 1 in 20,000. 6 Women are affected more than men in the ratio 1.5-2:1 and usually present with symptoms after menarche. Ms X had attained her menarche at 14 years of age. The majority of attacks are some appear to arise spontaneously. 7 The symptoms are episodic in nature. There is no proven explanation for the episodic pattern of these attacks. However, they are often provoked by drugs such as anticonvulsants, sulphonamides, oestrogen and progesterone, especially the oral contraceptive pill, or by number of cases, no precipitant can be 8 Ms X had underwent an episode of fasting for religious endowments , 24 hrs prior to both episodes of presentation, thus making fasting as a proven precipitating factor for an acute attack in her case.
Diagnosis of an acute porphyria attack is usually suggested by a triad of symptoms: visceral abdominal pain, neurological dysfunction and psychiatric disturbances, such as mental status changes. Of these, abdominal pain is the most troublesome for patients and is the most frequent cause of hospital admission. 9 Ms X presented with persistent abdominal pain and vomiting which is seen commonly in cases of acute intermittent porphyria.
Frequent spontaneous acute attacks have a highly variable course, lasting from several months to many years, and they are often associated with a markedly impaired quality of life. 10 As has been highlighted already that many of them present with Central Nervous System (CNS) manifestations during the acute attack, at least 20% of them with seizures, 11 Ms X also exhibited three episodes of seizures during her two episodes of acute porphyria presentation. Apart from seizures, her clinical examination revealed weakness in all upper and lower limbs, bilaterally.
Various literatures have described about the psychiatric comorbidities in cases of acute intermittent porphyria and vice versa. Psychiatric manifestations occur with a high prevalence and the clinical picture is usually colored with clouded consciousness, paranoid features and schizophrenia-likereactions. 12 Although psychiatric symptoms in AIP are common, cases with psychiatricsymptoms as the only manifestation are rare. 13 However in a study done by Kuhnel et al (2000), of hereditary coproporphyria attacks, 28% of patients presented with psychiatric symptoms. 14 Compared with individuals without manifest AIP, individuals with AIP had fourfold increased risks of being diagnosed with schizophrenia or bipolar disorder. Firstdegree relatives of individuals with AIP had double the risk of schizophrenia and bipolar disorder. 15 Suarez et al. reviewed medical histories of 1039 patients diagnosed with AIP reported in themedical literature and found that the most common psychiatric manifestations were delirium (22%), depression (8%) and psychosis (7%). 16 As reported by Millward, assessment of 90 patients with porphyria revealed anxiety as a relatively stable personality trait with 46% of the group reporting some problem with anxiety and depression. 17 Ms X exhibited symptoms of panic disorder.
Keen observation with high index of clinical suspicion, always surrounded by questions like "why is it happening"? "What could be the cause?" etc(which are the ornaments of a good and astute clinician),drove the team towards dedicated clinical discussions in this case (which should ideally be maintained in each and every patient) and was the key to diagnosis. This case also warns us not to make a psychiatric diagnosis in a haste or jump to psychiatric or functional diagnosis without a thorough and detailed assessment or without ruling out an organic cause.
We are still uncertain about what course this illness will take in future. Due to unavailability of genetic screening techniques, we have not been able to screen the family members. Owing to the high costs of investigations and considering the patient's low socio-economic background the management options remain limited. Owing to their social and poor to explain the disease process and offer any sort of reassurances, causing emotional setback among family members.

CONFLICT OF INTEREST: None.
CONSENT: NMJ case report consent form was signed by the patient.