New HMBS mutation found in woman with AIP and brain lesions

After six months, patient was fully recovered with no AIP recurrences

Joana Vindeirinho, PhD avatar

by Joana Vindeirinho, PhD |

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A Chinese woman with acute intermittent porphyria (AIP) accompanied by brain lesions was found to have a new mutation in the HMBS gene, a case report described.

Along with other symptoms including constipation, seizures, and muscle weakness, the woman had swelling in some areas of the brain, indicative of a brain condition called posterior reversible encephalopathy syndrome (PRES).

“AIP should be taken into consideration in the differential diagnosis of PRES and genetic testing is important for suspected AIP patients in confirming the diagnosis. Timely and accurate treatment of AIP may also improve disease prognosis,” the researchers wrote.

The case report, “Novel Mutation of Hydroxymethylbilane Synthase in a Case of Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome,” was published in the Journal of the College of Physicians and Surgeons Pakistan.

AIP, the most common form of acute porphyria, is caused by mutations in the HMBS gene. These mutations disrupt the production of heme, a key molecule for oxygen transport in cells, causing a buildup of heme precursor molecules in several tissues that can become toxic. AIP is characterized by a sudden, and sometimes severe, onset of symptoms.

A timely diagnosis and subsequent treatment of AIP can help prevent severe complications. However, because AIP symptoms are often nonspecific, patients can be misdiagnosed and the correct treatment can be delayed, with severe consequences.

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In this report, researchers described the case of a 23-year-old Chinese woman who first presented with episodes of constipation, abdominal pain, and convulsions lasting for more than four months.

She was initially diagnosed with intestinal obstruction. However, she continued to have seizures as the disease progressed. She also described having repeated occurrences of sudden and agonizing abdominal and femoral pain.

MRI brain scans revealed several lesions indicative of PRES, which “has been reported in very few patients with AIP,” the researchers wrote.

Clinical examinations revealed she had mild muscle weakness and some decreased tendon reflexes in the limbs, as well as high blood pressure, a slightly fast heart rate, low blood levels of sodium and hemoglobin (the protein in red blood cells that transports oxygen).

She continued experiencing recurrent and severe abdominal pain, but no clear cause for it was found. Furthermore, her urine had a strange color that would change to dark red when exposed to sunlight.

Taken together, these symptoms led doctors to suspect she might have AIP. A urine porphyria screening test, called the Watson-Schwartz test, came back positive, confirming the diagnosis.

Improvement in condition with glucose infusions, treatments for symptoms

She was given glucose infusions and treatments to control her symptoms, and her condition started to improve gradually. After six days of treatment, her PRES lesions were reduced and after six months, she had fully recovered. No AIP recurrences occurred up to the publication date of the case report.

A genetic test showed she had a previously undocumented mutation in the HMBS gene called c.1005dupC (p.I336Hfs*23), which might affect the activity or stability of the resulting protein. Computer analysis of the mutation deemed it to be pathogenic, or disease-causing, leading researchers to hypothesize the mutation was probably related to her AIP attack.

“Molecular genetic testing offers an accurate diagnosis and typing for symptomatic patients, which can then be applied to the identification of AIP among relatives,” the researchers wrote.

In this case, the patient’s family refused genetic testing, so doctors provided them with information on the risk factors that might trigger an AIP attack, such as certain medications or environmental factors.