Prolonged AIP treatment helps woman recover after severe attack

A woman with acute intermittent porphyria (AIP) who suffered an unusually severe attack marked by extensive muscle breakdown, kidney injury, profound weakness in all four limbs, and respiratory failure was helped by long-term treatment, according to a case report from Croatia.

Treatment with hemin followed by long-term Givlaari (givosiran), together with physical rehabilitation, resulted in a slow but substantial neurological recovery.

After more than two years of Givlaari treatment, the woman was able to walk and had experienced no further acute attacks while receiving monthly therapy. When the interval between Givlaari doses was extended to every two months, however, she developed another, milder AIP attack.

“Our case illustrates that treatment with hemin and givosiran for longer than two years may be needed for neurological recovery after an AIP attack with severe motor polyneuropathy [nerve damage] and multisystem involvement,” the researchers wrote.

The report, “Acute intermittent porphyria presenting with rhabdomyolysis and polyneuropathy with severe quadriparesis and respiratory failure: A case report,” was published in the World Journal of Critical Care Medicine. 

Attacks can be painful

AIP is the most common type of acute porphyria, a group of rare inherited disorders affecting the production of heme, a molecule needed for oxygen transport in living cells. In AIP, reduced activity of the enzyme hydroxymethylbilane synthase can cause toxic heme-building molecules, including aminolevulinic acid (ALA) and porphobilinogen (PBG), to accumulate. These can damage the nervous system during an acute attack.

Attacks often result in porphyria symptoms including severe abdominal pain. They may also involve nausea, constipation, rapid heartbeat, high blood pressure, and neurological symptoms. Severe attacks can cause seizures, brain dysfunction, and damage to peripheral nerves that control movement.

Clinicians described a particularly severe AIP attack complicated by rhabdomyolysis — the rapid breakdown of skeletal muscle that can release damaging substances into the blood — and severe motor nerve damage.

The 28-year-old woman went to the hospital with abdominal pain, generalized weakness, muscle aches, and reduced urine output. She had recently completed an antibiotic course for a presumed urinary infection, which the authors considered a possible trigger for the attack.

Tests showed severe rhabdomyolysis and acute kidney injury requiring dialysis, a medical procedure that’s used to filter waste products and excess fluid from the blood when the kidneys can no longer perform their normal function.

Her weakness rapidly worsened into severe quadriparesis, marked weakness of all four limbs. She also developed hallucinations and weakening of the muscles needed for breathing, ultimately requiring prolonged mechanical ventilation.

An important diagnostic clue was dark red urine without significant blood. Urine tests revealed markedly elevated levels of ALA and PBG, confirming an acute porphyria attack, and genetic testing later identified a disease-causing mutation in the HMBS gene.

She initially received into-the-vein hemin and glucose. Because porphyria-related markers rose sharply whenever clinicians tried to stop or reduce hemin, treatment continued for about three and a half months. However, prolonged hemin raised concerns about iron overload, prompting a switch to monthly Givlaari.

After three months, the woman no longer required breathing support, and at six months, she could walk using crutches. Over more than two years of monthly Givlaari and rehabilitation, her strength continued to improve until she regained near-complete mobility, with only mild residual weakness in her feet and thumbs.

An attempt to administer Givlaari every two months led to a new, mild attack, which was treated with three hemin infusions, after which monthly dosing resumed. The researchers also noted worsening chronic kidney disease during follow-up, although they could not determine whether this was related to AIP, Givlaari, or both.

The authors stressed that rhabdomyolysis may be overlooked during severe AIP attacks because muscle weakness and dark urine can occur with either condition. They suggested checking muscle injury markers in severe attacks and considering AIP when unexplained rhabdomyolysis occurs.