# A New Generation of Porphyrias: A Case of Acute Intermittent Porphyria

## TL;DR

A 41-year-old woman with a history of acute intermittent porphyria (AIP) experienced a severe crisis involving neurological and systemic symptoms, diagnosed through lab tests and genetic analysis.

## Contribution

The paper reports a novel pathogenic variant (p.Leu42Ser) in the HMBS gene associated with AIP and emphasizes the importance of early diagnosis and new treatment options.

## Key findings

- A heterozygous variant p.Leu42Ser in the HMBS gene was identified as likely pathogenic in the patient.
- Prompt treatment with hematin resolved the patient's symptoms within four days.
- The case highlights the need for high suspicion and early diagnosis in patients with a history of AIP.

## Abstract

Porphyria refers to metabolic disorders caused by dysfunctional heme biosynthesis. Acute intermittent porphyria (AIP) is the most common and severe form of acute porphyria, inherited in an autosomal dominant pattern. During a crisis, diagnosis can be established by collecting urine, plasma, and stool samples for work-up, and treatment should be started.

We report the case of a 41-year-old female patient with a known history of AIP and prior recurrent crises, presenting with severe intracranial hemorrhage due to aneurysm rupture secondary to a hypertensive emergency at the age of 38. She presented to the Emergency Department with nausea, vomiting, abdominal and lower limb pain, left upper and lower limb paresthesias, anxiety, and insomnia. A positive Hoesch test led to a presumptive diagnosis of AIP crisis. Fecal and urinary laboratory work-ups were compatible with an AIP crisis. Genetic studies for new generation porphyrias identified a heterozygous variant p.Leu42Ser in the hydroxymethylbilane synthase (HMBS) gene, probably a pathogenic variant. She completed four days of treatment with hematin, with complete resolution of pain. We highlight the need for prompt evaluation and diagnosis of an AIP crisis, particularly in patients with a known personal or family history of AIP. New therapeutic alternatives with minor side effects are now available and should be started as soon as possible. Given that symptoms are often nonspecific and variable, there should be a high index of suspicion in these patients.