Acute intermittent porphyria caused by novel mutation in HMBS gene, misdiagnosed as cholecystitis

Abstract

BackgroundAcute intermittent porphyria (AIP) is an autosomal dominant neurovisceral inherited disorder due to a defect in the heme biosynthesis pathway. Misdiagnosis of the porphyrias is not uncommon.Case reportWe present a case of a 26-year-old female with suspected acute cholecystitis, mental status changes, and seizures. Biochemical and molecular investigations confirmed the diagnosis of AIP by findings of elevated urinary porphobilinogen, 5-aminolevulinic acid, and total porphyrins. DNA molecular testing showed a novel heterozygous mutation (c. 760delC p.L254X) in the exon11 of the HMBS gene. To the best of our knowledge, this is the first report of a misdiagnosis of AIP presenting with acute cholecystitis.ConclusionClinicians are alerted to consider the possibility of AIP in an adult presenting with an acute abdomen, features of cholecystitis, and neuropsychiatric manifestations.

Acute intermittent porphyria after right hemi-colectomy

“…Similar to our case, the classical patient of AIP is a woman in her third decade of life [3], [5], [6], [7], [8]. Abdominal pain is the most common severe presentation of AIP being present in 85%-95% of patients.…”

“…Abdominal and brain CT scan and MRI, gastro-intestinal endoscopy, CSF analysis, electromyography and nerve conduction studies are usually normal or non-specific [1], [3], [4], [6], [7], [10], [13]. The diagnosis of AIP is based on elevated levels of urinary PBG (as in our patient) and 5-aminolevulinic acid (ALA) and confirmed by DNA study for hydroxymethylbilane synthase (HMBS) gene mutations [1], [2], [3], [8].…”

“…At times, peripheral motor neuropathy can lead to paralysis and respiratory failure mandating mechanical ventilation for few days [3], [4], [8], or several months [7]. We believe that our patient improvement is attributed to the good ICU management and high caloric intake before establishing the diagnosis of AIP.…”

“…In Saudi Arabia, there is no data on the incidence of AIP and only one case was reported concerning a young woman with AIP mimicking acute cholecystitis [8] .…”

A novel 55-basepair deletion of hydroxymethylbilane synthase gene found in a Chinese patient with acute intermittent porphyria and her family

“…Patients in acute attacks typically present 3 dominated clinical manifestations (acute abdominal pain, peripheralor spinal neuropathy, and psychiatric disorders), resulted from the redundancy of the porphyrin precursors. A total of 95% patients with acute onset have severe but poorly localized abdominal pain and may be wrongly diagnosed as “acute abdomen,” such as appendicitis, cholecystitis, etc., [ 5 , 9 ] as is in our case. The patient's first chief complaint was acute abdominal pain with other typical symptoms including nausea, vomiting, constipation or diarrhea, tachycardia, and hypertension.…”