A 16 years old female, was referred to Pakistan Institute of medical sciences Islamabad, from a private setup in Gilgit Baltistan for management of acute abdomen. She developed severe abdominal pain while on her way to the school and was perfectly alright before that. There was no history of nausea, vomiting, dyspepsia or fever associated with the abdominal pain. Examination at the time of arrival was unremarkable except for diffusely tender abdomen. While she was investigated, supportive treatment in the form of intravenous fluids, proton pump inhibitors and antibiotics were started.
Her laboratory investigations were unremarkable except for a White blood cell count of 11000/mcl. Her ultrasound abdomen and x-ray erect abdomen was also unremarkable. CECT abdomen and pelvis showed non-specific mesenteric lymphadenopathy. During her stay in the hospital, she developed generalized tonic-clonic seizures. Her blood sugars and serum calcium levels were done which were normal but she had severe hyponatremia of 105 mEq/L. The neurology department was consulted and she was started on anti-epileptics. For workup of hyponatremia, a medical consult was sought.
Before going on to the workup advised by the medical team, lets scratch our heads to diagnose this patient.
- What workup may be advised at this stage?
- What is the possible diagnosis?
- How will you manage this patient?
Students should try to make a diagnosis or differential diagnosis before reading the discussion below.
Follow-up of our patient …
When we first saw the patient, she was afebrile, conscious and obeying commands at that time. She had a soft and non-tender abdomen. The following things were kept in mind while we started investigating her:
- What is the cause of hyponatremia? Is it renal wasting or a gut pathology? Is it SIADH?
- What is the underlying diagnosis?
Her urinary and serum electrolytes were sent which suggested SIADH (high urinary sodium, low plasma osmolality, and high urinary osmolality. She was started on a calculated dose of hypertonic saline and free water restriction.
Since a surgical cause of the acute abdomen was ruled out, and medical causes of the acute abdomen are very few, acute intermittent porphyria was our presumptive diagnosis. The patient was asked to collect her urine and keep it in sunlight for sometimes. Her urine for porphobilinogen was also sent.
Urine color of the patient turned reddish-brown on exposure to sunlight and her urine for PBG was strongly positive as well. She was started on dextrose water with saline and her anti-epileptics were stopped. She rapidly improved and was discharged with the instructions to avoid certain medications.
Acute intermittent porphyria:
Pattern of Inheritance: Autosomal dominant
Enzyme deficient: PBG deaminase (porphobilinogen deaminase)
Clinical features of AIP – remember abdominal pain:
Acute intermittent porphyria as the name suggests is characterized by intermittent attacks of symptoms with rapid onset of symptoms, hence the term “acute”. Sypmtoms may be visceral, autonomic, psychiatric or neurological and peripheral.
Abdominal pain is the most common symptom. It is usually severe but tenderness, fever and leukocytosis are minimal. The pain may mimick acute appendicitis, mesenteric ischemia, and as acute surgical abdomen. Infact, surgical exploration is the fate in many patients who present with abdominal pain.
other symptoms include numbness, paraesthesias and neuropathy. Motor weakness usually starts in the proximal muscles and progress to distal muscles.
Patients may present with bladder dysfunction, constipation or diarrhea. The Urine changes its color to black or reddish-brown on exposure to sulight. Other patients may develop hallicination, agitation and depression.
Some patients may develop hyponatremia and hypomagnesemia. Hyponatremia is usually due to the syndrome of inappropriate anti-diuretic hormone. Patients may also have fluctuating blood pressure or may develop hypertension.
In patients with bulbar and respiratory muscles involvement, AIP may be life threatening.
Diagnosis of Acute intermittent porphyria:
Urine for PBG is the most cost-effective test to diagnose AIP. PBGD deficiency may be identified via DNA testing after the diagnosis of AIP.
Treatment of AIP:
Hospitalization is usually required for acute attacks.
Patients should be monitored for respiratory failure. Electrolytes and nutritional status should be assessed and managed accordingly.
Tachycardia and hypertension may be treated with propranolol. Pain and nausea may require narcotic analgesics and ondansetron.
Almost all anti-epileptics are known to exacerbate the condition. Hyponatremia may require hypertonic saline and free water restriction. Similarly, patient with seizures and hyponatremia, should be managed with hypertonic saline first. If, the seizures are still not controlled after the correction of hyponatremia, clonazepam may be used as an anti-epileptic.
Attacks should be treated with carbohydrates and hemin.
Liver transplantation is very effective but there have been reports of worsenig neurological symptoms after liver transplantaiton.
patient should be advised to take high carbohydrate diet, avoid oral contraceptive pills and most of the neuropsychiatric medicines.