Severe Neuropathy Could Be Sign of Acute Intermittent Porphyria

Rapid and severe damage to peripheral nerves, those sending sensory and motor information from the brain and spinal cord to the rest of the body, can be a rare sign of acute intermittent porphyria (AIP), a case report suggests.

Early diagnosis of AIP is key in avoiding serious nerve damage, the scientists said.

The report, “Severe neuropathic attack in a woman with acute intermittent porphyria: a case report,” was published in the Journal of International Medical Research.

AIP is characterized by low levels of the enzyme hydroxymethylbilane synthase, due to mutations in the HMBS gene. This enzyme is involved in the production of heme, the component of red blood cells that binds to and carries oxygen throughout the body.

This deficiency causes porphyrins to accumulate inside cells, including in nerve cells. Between 10 to 40% of patients experience AIP attacks affecting the peripheral nervous system, with most being of mild intensity.

Researchers in China reported the case of a woman, later found to have AIP, who showed severe and quickly progressing damage to her peripheral nerves, a condition called peripheral neuropathy.

The 37-year-old was admitted to the hospital with abdominal pain and bloating, which had been bothering her for the previous four months. She had been taking traditional Chinese medicine, as well as analgesics, to treat the discomfort, but was not improving.

X-rays done after her admission showed an incomplete intestinal obstruction. Two days later, she began experiencing shortness of breath, muscle weakness, hypoxemia (low oxygen levels), a fast heart rate, and low blood pressure.

She was transferred to the intensive care unit (ICU), while showing severe hypoxemia and respiratory acidosis (the result of poor lung function, causing the blood to become acidic). She underwent tracheal intubation, a procedure in which a flexible plastic tube is placed in the windpipe to maintain an open airway.

Her symptoms eased within two days. But muscle weakness was still severe, and she still needed breathing support. Sensory nerves were normal upon examination.

A chest X-ray scan showed fluid in the lower area of the lungs, but this could not explain her respiratory failure, the scientists noted. Blood tests showed high levels of creatinine and urea nitrogen, indicative of kidney problems. However, these levels normalized after hemodialysis, given to filter waste and water from the blood as the kidneys would do.

No autoreactive antibodies indicative of peripheral neuropathy were found in the cerebrospinal fluid, which surrounds the brain and spinal cord.

An electromyography, used to assess the health of muscles and nerves, showed signs of peripheral nerve damage. At this stage, the woman was diagnosed and started treatment for Guillain-Barré syndrome, a neurological disease in which the body’s immune system attacks nerve cells.

Her condition to worsen. Two weeks into her intensive care stay she again experienced abdominal pain, constipation, and general weakness.

An examination of the cranial nerves showed alterations affecting the nose and lips; the patient was no longer able to close her eyelids. Urine color was found to turn reddish upon exposure to sunlight.

The woman was now diagnosed with AIP, which was confirmed by a genetic analysis showing a mutation in the HMBS gene.

“Between 10% and 40% of patients with porphyria may exhibit symptoms of peripheral nerve damage during an AIP attack,” the researchers wrote, but “such patients are usually mildly affected. It is rare for a patient to experience severe peripheral nerve damage.”

Since heme arginate, a medication that lowers the production of porphyrins, is not available in China, she was treated with blood infusions of glucose to lower porphyrin production in the liver. Her urine color returned to normal within 24 hours, and her abdomial pain lessened. Her peripheral neuropathy, however, showed no improvement.

The breathing tube was removed after two weeks, and she was transferred to a local hospital for muscle rehabilitation. At a  follow up visit one year later, the patient was able to walk with assistance and her muscle strength had improved. No other AIP attacks were reported through to the study’s conclusion, but she still had severe neurological damage.

“When a patient presents with severe progressive neuropathy, AIP should be taken into consideration, despite the appearance of symptoms of common diseases in the ICU,” the researchers wrote.

“Early diagnosis can avoid serious peripheral nerve damage, prevent recurrent episodes, and even save lives,” they concluded.