Acute porphyria may first appear as new-onset psychosis, case shows

A 67-year-old man with no psychiatric history was initially treated for mania with psychotic symptoms before abdominal pain, neurological symptoms, and dark urine prompted testing that supported a diagnosis of acute porphyria, a case report describes.

One of his initial medications, valproic acid, can trigger or worsen porphyria attacks and was discontinued once porphyria was suspected. The man’s physical and psychiatric symptoms ultimately resolved, and he remained free of psychosis during two years of follow-up.

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This case highlights how acute porphyria can cause prominent psychiatric symptoms before more characteristic physical and neurological symptoms emerge and “underscores the importance of recognizing” neuroporphyria, as well as the need “for comprehensive evaluation and timely intervention to mitigate potential adverse outcomes,” researchers wrote.

The case report, “King George’s Psychosis: A Case Report of Neuroporphyria in an Acute Psychiatric Inpatient Unit,” was published in the journal Cureus.

Porphyrias are a group of rare metabolic disorders caused by defects in heme production. Heme is a molecule used to make hemoglobin, the protein that enables red blood cells to carry oxygen, as well as other proteins. When heme production is disrupted, substances produced earlier in the process can accumulate and cause symptoms.

Neuroporphyrias are porphyrias that cause neurological and psychiatric symptoms when toxic substances produced during heme production build up in the nervous system. Acute intermittent porphyria (AIP), the most common type of neuroporphyria, typically causes severe abdominal pain, nervous system symptoms, changes in heart rate or blood pressure, and psychiatric symptoms. In some cases, psychiatric symptoms may be the predominant or even sole manifestation.

Because its symptoms can overlap with those of other conditions, acute porphyria can be difficult to recognize, particularly when a patient has no known family history of the disease.

Here, clinicians in Portugal described a case that illustrates how difficult acute porphyria can be to diagnose when psychiatric symptoms appear first and highlights the importance of considering an underlying medical cause when new-onset psychosis is accompanied by atypical features.

Behavioral changes progressed over two months

The man, age 67, had no previous psychiatric history when progressive behavioral changes began. Over about two months, he became increasingly irritable and developed grandiose speech and delusions, including claims that he had connections to prominent public figures.

When he was brought to an emergency department for psychiatric evaluation, he was severely agitated and uncooperative and showed rapidly shifting thoughts and grandiose delusions. He was involuntarily admitted with a provisional diagnosis of mania with psychotic symptoms and started on the mood stabilizer valproic acid and the antipsychotic risperidone.

Soon after admission, he developed sudden abdominal pain, fever, high blood pressure, a rapid heartbeat, tingling or other abnormal sensations in his legs, and urine that appeared reddish-brown to dark green. Blood tests also revealed low potassium, signs of inflammation, and evidence of liver injury.

The combination of new physical and neurological symptoms prompted an internal medicine evaluation. Clinicians considered acute neuroporphyria as well as other possible causes, including lead poisoning, Wilson’s disease (when the body cannot properly get rid of excess copper), and hemochromatosis, a condition in which the body absorbs too much iron from food. Brain imaging was unremarkable, and further testing ruled out the other suspected causes.

Once acute porphyria became a leading possibility, valproic acid was gradually discontinued because the medication is porphyrinogenic, meaning it can trigger or aggravate porphyria attacks. Several other psychiatric medications, including barbiturates, carbamazepine, and tricyclic antidepressants, can also trigger or worsen attacks, the authors noted.

The patient’s physical symptoms began to ease, although his delusions initially persisted.

Delayed testing still supported acute porphyria

Specialized tests for porphyria were not routinely available at the hospital, and samples were collected after the acute phase had already subsided.

Despite the delayed testing, urinary levels of porphobilinogen (PBG), a compound produced during heme synthesis that can rise during acute porphyria attacks, were elevated, supporting the diagnosis.

PBG and delta-aminolevulinic acid (ALA) are heme-pathway precursors commonly measured in random urine samples when acute porphyria is suspected. The authors noted that testing during an active attack is particularly important for distinguishing among neuroporphyrias, while genetic testing is recommended for confirmation.

Because the man’s delusions continued after his physical symptoms eased, clinicians switched his antipsychotic medication from risperidone to paliperidone, which the authors considered to have a more favorable safety profile in porphyria. He progressively achieved full remission of his psychotic symptoms and was discharged after 48 days.

During the following two years, he remained free of psychotic symptoms. His antipsychotic medication was gradually tapered and eventually stopped, with no recurrence of psychotic symptoms reported.

Overall, the case highlights the need to investigate possible medical causes when psychosis first appears later in life, particularly when it occurs alongside abdominal pain, neurological symptoms, changes in heart rate or blood pressure, or reddish-brown or dark urine.

Recognizing porphyria is particularly important because misdiagnosis may expose patients to medications that can worsen an attack.

“Clinicians should maintain a high index of suspicion for porphyria in new-onset psychosis with atypical features,” the authors concluded.