Late AIP diagnosis leads to severe disability in young woman

Case illustrates how disease's nonspecific symptoms can result in missed diagnosis

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An illustration shows a woman sitting on a bed, holding her abdomen in pain.

An early diagnosis and treatment for acute intermittent porphyria (AIP) might have prevented severe complications in a 21-year-old woman, according to a U.K. case report.

The researchers noted the nonspecific symptoms of porphyria attacks may make the diagnosis difficult. However, recurrent abdominal pain, low sodium levels in the blood, and neurological symptoms in a young adult are highly suggestive of acute porphyria.

“With the help of this case, it is highlighted how important it is to keep this condition in mind in young patients, especially females, with unexplainable severe abdominal pain as there is a risk of severe disability,” the researchers wrote in the case study, “A Case of Acute Intermittent Porphyria Leading to Severe Disability in a Young 21-Year-Old Female,” which was published in Cureus.

Porphyrias are genetic disorders caused by disruptions in the heme production cycle. Heme is a molecule that plays a key role in oxygen transport in living cells. The loss or dysfunction of specific enzymes involved in heme production leads to heme precursors accumulating in different tissues, mainly the liver and skin.

AIP, the most common acute porphyria, is marked by sudden, sometimes severe, attacks involving several organs. It’s caused by a mutation in the gene encoding hydroxymethylbilane synthase, a key enzyme in the heme production cascade. The disease is more common in women in their late teens to early 30s.

Diagnosing AIP can be challenging considering its symptoms are nonspecific. Delays in identifying and treating the disease attacks, however, may lead to severe complications, such as motor neuropathy, seizures, psychosis, and low blood sodium levels (hyponatremia). Motor neuropathy is a condition wherein the nerves that control voluntary muscle movements become damaged, leading to muscle weakness.

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AIP Patient, 21, Successfully Treated Despite Delays Due to Misdiagnosis

Diagnosis of acute intermittent porphyria

Researchers reported the case of a young woman who developed several complications after going more than a year before being diagnosed.

The 21-year-old patient went to the hospital due to severe and constant abdominal pain for a week, accompanied by pain and discomfort when urinating.

She had been evaluated for abdominal pain eight times in the emergency department during the previous year. In a previous evaluation, blood tests and CT scans of the abdomen and pelvis were normal. At her admission, a physical examination and blood tests of cell counts, electrolytes, and liver and kidney function were normal.

An endoscopy showed signs of gastritis — a condition wherein the lining of the stomach is inflamed — and the woman was discharged with instructions to take analgesics for pain relief, a proton pump inhibitor to lower stomach acid production, and antibiotics for urinary tract infections. An endoscopy lets clinicians view the inside of the stomach with a flexible tube inserted into the mouth.

Two months before being admitted, she developed limb weakness with recurrent falls that led to bruising on her upper and lower limbs.

At admission, she had a fast heart rate and muscle weakness in the right upper arm, consistent with motor neuropathy.

Routine blood tests showed low sodium levels, which, with recurrent abdominal pain, neuropathy, and neuropsychiatric symptoms, led doctors to suspect AIP.

An urine test showed her levels of porphobilinogen (PBG), a heme precursor, were very high, confirming a porphyria diagnosis.

Deteriorating condition underscores importance of early diagnosis

The woman’s condition deteriorated. She went into respiratory failure and was moved to the intensive care unit, where she was intubated and put on a ventilator under sedation.

She was also started on heme arginate, a medication sold under the brand name Normosang and commonly used as a first-line treatment for severe porphyria attacks. It’s approved in Europe, but not licensed in the U.S.

An initial attempt to remove her from ventilation failed, as she still showed signs of motor neuropathy and respiratory impairment. She was re-intubated and a tracheostomy was later required along with into-the-vein nutrition due to her difficulty swallowing. A tracheostomy is a procedure to open a hole in the windpipe to create an alternative airway for breathing.

The woman had recurrent acute attacks that were managed with heme arginate over the next four weeks. She started monthly treatment with Givlaari (givosiran) to control the attacks, which seemed to delay her neurological recovery.

She continued supportive management, including intensive physiotherapy sessions. After 37 days at the intensive care unit, the woman regained control of her head and shoulders and was able to flex her hips. She remained in bed because she couldn’t bear any weight, however. She had no further porphyria attacks and her abdominal pain resolved.

After almost three months of acute care, her tracheostomy was reversed and she was transferred to inpatient neuro-rehabilitation.

“Our case is a clear example of how severely AIP can affect a patient’s mental and physical status and emphasizes how important is to make early diagnoses that could effectively have prevented significant disability,” the researchers wrote. “When attacks do occur, the nonspecific presentation compounds the diagnostic challenge. However, the combination of abdominal pain (particularly when recurrent) with hyponatremia and neurological manifestations in a young adult is strongly suggestive of acute porphyria. Early diagnosis and commencement of treatment may prevent severe complications.”