A new case report illustrates common misdiagnosis given, and lack of awareness among clinicians, that may cause severe complications to patients with acute intermittent porphyria (AIP).
The study, “Many pitfalls in diagnosis of acute intermittent porphyria: a case report,” appeared in the journal BMC Research Notes.
The most frequent manifestation of AIP is severe abdominal pain. In acute attacks, patients exhibit neurovisceral manifestations, such as constipation, muscle weakness, vomiting or diarrhea. However, as these are common to several other conditions, AIP diagnosis may be challenging.
Researchers discussed the case of a 33 year-old man from Sri Lanka who arrived at the hospital after three days of neurovisceral problems – the most common clinical manifestation of AIP – that included intermittent abdominal pain, nausea, vomiting, constipation, and numbness in both lower limb extremities. The patient was treated for possibly having as= partial intestinal obstruction, while a diagnostic evaluation through laparoscopy surgery was awaited.
He subsequently showed evidence of confusion and systemic (generalized) hypertension was detected, which led to his transfer to a medical ward. The patient was non-diabetic and had no history of hypertension. He had been taking over-the-counter analgesics for six weeks.
He had similar neurovisceral attacks that necessitated five hospital admissions over two years, leading to diagnoses of appendicitis, sinus tachycardia (a faster than usual heart rate), renal colic, interstitial nephritis (a form of kidney inflammation), and partial intestinal obstruction.
Evaluations following these attacks did not support a diagnosis of intra-abdominal pathology (disease inside the abdomen). The sixth attack made clinicians suspect acute porphyria.
The patient was thin and pale, and had a 160/90 mmHg blood pressure, consistent with hypertension. Test of muscle strength in all four limbs revealed he could not move against good resistance.
Laboratory examinations showed severe hyponatremia, or low blood sodium level. His serum osmolality – a measurement of the amount of molecules in the blood – and concentration of hemoglobin, the protein carrying oxygen in the blood, were lower than normal. Total cholesterol, LDL, and serum ferritin — a protein that stores oxygen in tissues — were high.
Additional exams suggested metabolic acidosis – an increase in the amount of acid – and right ventricular hypertrophy (enlargement).
The patient’s urine sample gradually turned dark brown on standing. Analysis showed that the total porphyrin level was 5505.5 nmol/L, much higher than the threshold for normal values (under 300 nmol/L). The Watson and Schwartz test of porphobilinogen, an intermediate in the synthesis of porphyrins, was positive.
Genetic analysis showed a previously reported mutation in HMBS, the gene whose alterations cause AIP. This specific mutation, known as R173W, is likely to have increased severity, according to the researchers. Four of five first-degree relatives were heterozygous (only one gene copy affected) for the same mutation.
The patient was then managed for symptoms, as treatment with heme arginate is not available in Sri Lanka. Clinicians treated him with carbohydrate (sugar) loading with intravenous dextrose (a form of glucose) and oral carbohydrates.
He was discharged as symptoms improved over six days. Monitoring of treatment response through urinary sample analysis could not be conducted as it is unavailable and cost prohibitive in Sri Lanka, the scientists said.
He continued to be followed at a clinic with regular monitoring of kidney function, hemoglobin concentration, and blood pressure. He had two more attacks within one year, but did not required hospitalization.
Overall, this case illustrates the underdiagnosis and frequent misdiagnoses given to patients with AIP, which lead to poor disease management and severe complications.
Correct diagnosis enables “implementation of strategies to prevent acute attacks, and also triggers screening and genetic counseling of at-risk family members,” the researchers wrote.“Therefore, a high index of suspicion and awareness of front line laboratory investigations is important for appropriate diagnosis.”