Acute intermittent porphyria (a report of two cases).
Acute intermittent porphyria (AIP) is a rare hereditary disorder of porphyrin metabolism characterised by episodes of severe abdominal pain, rapidly progressive flaccid paralysis and passage of excess amounts of porphobilinogen (PBG) in urine., Abdominal pain in AIP may simulate acute surgical abdomen leading to an unwanted laparotomy. Rarely, generalised epileptic fits and neuropsychiatric disturbances may occur., We report here two cases of AIP due to its rarity with a brief resume of relevant literature to highlight its presenting symptoms and importance of prophylaxis.
A 25 year old male was referred to the University Hospital, Varanasi and was admitted on 6th October, 1982. In February 1982, he had the first episode of severe abdominal pain around the umbilicus, stabbing in character which radiated towards the back and persisted for about 3 weeks. After the pain subsided, he developed acute onset, rapidly progressive weakness in all the four limbs and got bed-ridden within 4 to 5 days. From this, he gradually improved over a period of one month. He remained asymptomatic for approximately 3 months. In August, 1982, he had second episode of similar abdominal pain which persisted for about 2 weeks following which he developed rapidly progressive weakness. It started in the right upper limb followed by the left upper limb and then affected both the lower limbs. Weakness progressed for about a week when he got bed-ridden. He also developed difficulty in closing the lips and eyes and salivation from the angles of the mouth. He denied any history of paraesthesia, sphincteric disturbances, epileptic fits or dark coloured urine during any of the episodes. No definite history of any drug intake prior to both the episodes could be ascertained.
Examination revealed bilateral facial palsy of lower motor neuron (LMN) type together with flaccid quadriparesis which was more marked distally with bilateral wrist drop. There was no sensory loss.
His total leucocyte count was 8,900/cmm, with differential count of P-60%, L-36% and E-4%. Hemoglobin was 12 gm% and ESR, 35 mm in the 1st hour. Urine was positive for PBG. Cerebrospinal fluid (CSF) was normal. Nerve conduction velocity (NCV) revealed diffuse neuropathic changes.
The patient was given symptomatic- treatment along with general supportive measures and showed gradual improvement.
A 14 year old male presented with one week history of episodic severe abdominal pain associated with vomiting 3 to 4 times a day and dark reddish urine. He developed rapidly progressive weakness in all the four limbs for 2 days prior to hospitalization. In the past, he had 2 episodes of similar abdominal pain along with altered sensorium and generalised epileptic fits but without any weakness of limbs.
Examination revealed a fully conscious, thin built patient with normal pulse and blood pressure. Abdominal examination did not reveal any abnormality. Neurological checkup showed features of flaccid quadriparesis with bilateral foot drop. There was no sensory impairment.
Laboratory investigations showed the TLC of 11,300/cmm with a DLC of P-77%, L-19%, E-3% and M-1%. His hemoglobin was 13.5 gm% and ESR, 27 mm in the 1st hour. Urine was strongly positive for PBG. Urine samples of his parents and sisters were negative for this pigment. CSF was nomal. NCV showed features of diffuse neuropathy.
He was treated with chlorpromazine, 50 mg three times a day together with other general supportive and symptomatic measures. He had remarkable improvement within a week's time. At the time of discharge from the hospital, the patient was given a card regarding the diagnosis and list of common drugs known to precipitate the acute attacks of porphyria.
Acute attacks of AIP are often precipitated by drugs like barbiturates, sulfonamides, sulfones, chloroquin, griseofulvin, diphenyl hydantoin and many other drugs, acute infections and over-indulgence in alcohol., However, in none of our patients could the history of any precipitating factors be ascertained. Acute attacks are due to greatly increased activity of delta-aminolaevulinic acid synthetase. During acute attacks, the urine contains large amounts of porphobilinogen (PBG) and delta-aminolaevulinic acid (ALA) which, on standing, gives dark "port-wine" colour to the urine as was observed in our Case 2. Mental disturbances during acute episodes are of metabolic origin whilie neurological weakness of the extremities is due to focal demyelination and/or axonal degeneration of peripheral and autonomic nerves.
Onset of symptoms usually occurs in adolescence. Females are more commonly affected than males. However, our both the patients were males. The clinical picture is dominated by gastro-intestinal and neurological manifestations. Symptoms during acute episodes usually comprise of severe colicky pain in the abdomen which may be diffuse or localized-usually to the umbilical or epigastric region and is often associated with nausea and vomiting and occasionally diarrhoea., Diagnosis in such patients may be missed, unduly delayed or confused with acute surgical abdomen especially if neurological manifestations are lacking. Gastro-intestinal manifestations are related to severe intestinal spasm due to autonomic dysfunction. Neurological manifestations comprise of flaccid paralysis, neuropsychiatric disturbances and rarely generalised epileptic fits., Paralysis may be confined to lower or upper extremities or may affect all the four limbs. It may be more marked proximally or distally or may be generalised and is due to predominant motor neuropathy. Sensory symptoms may also occur but objective sensory loss is unusual. Both of our patients had motor neuropathy with predominant distal involvement without any sensory loss. Epileptic fits in AIP have been reported in about 15 to 20% cases., Our Case 2 had two episodes of generalised epileptic fits with severe abdominal pain and dark coloured urine and subsequently developed flaccid quadriparesis. Half of the patients may have involvement of cranial nerves. Our Case 1 had bilateral facial palsy of LMN type. Bulbar paralysis and respiratory involvement can also occur and may threaten the life of the patient., Sphincteric disturbances are uncommon. Skin lesions are seldom seen.
Diagnosis of AIP should be suspected in any patient presenting with rapidly progressive flaccid paralysis with severe abdominal pain and history of passing dark reddish urine. Examination of the urine during acute attacks for PBG and ALA will help in establishing the diagnosis. In our patients, the diagnosis of AIP was based on clinical and urinary findings.
There is no specific treatment for porphyria and it is therefore very important to prevent the onset of acute attack. Treatment during acute episodes usually comprises symptomatic and general supportive measures for bulbar and respiratory paralysis, if it occurs. Chlorpromazine has been reported to be beneficial in relieving pain and other symptoms. Approximately 25% sibs of patients of AIP may be expected to have PBG in urine and therefore screening of sibs and other family members should be done. Prophylaxis in such cases as well as those known to clinically manifest AIP includes the avoidance of drugs known to precipitate the acute attacks as enlisted above.