Case report highlights urgency in diagnosing acute porphyric crisis
Unusual mix of symptoms delayed diagnosis, treatment of variegate porphyria
While treating a woman in her 70s for a severe bacterial infection, clinicians came up with new ways to confirm the diagnosis of an acute variegate porphyria (VP) crisis when standard diagnostic tests were not feasible, which had also led to a delay in the patient’s treatment.
The woman’s unusual combination of symptoms, including neurological dysfunction, organ failure, and anuria (reduced ability to produce urine), prevented doctors from using tests commonly used in the diagnosis of porphyria, and prompted them to resort to other types of tests. Despite aggressive treatment, the woman eventually died from her illness.
“Progressive neurological compromise, coupled with undifferentiated multiorgan failure, should prompt consideration of an underlying acute porphyric crisis,” researchers wrote.
The study, “Diagnostic and Therapeutic Challenges in an Acute Variegate Porphyric Crisis Complicated by Anuric Renal Failure and Multiorgan Dysfunction: A Case Report,” was published in the American Journal of Case Reports.
VP and other types of porphyria are genetic disorders that disrupt the production of heme, a molecule that helps transport oxygen in the body. In people with porphyrias, the molecules used to make heme — porphyrins and their precursors — accumulate to toxic levels in different parts of the body, causing a wide array of symptoms.
Variegate porphyria most common in people of South African, Dutch ancestry
Acute attacks, often including pain and neurological symptoms, occur in VP, which is most commonly seen among people of South African and Dutch ancestry. Samples of urine, blood, or stool can be used to measure the levels of porphobilinogen (PBG), a porphyrin precursor, to diagnose VP during an attack.
In this study, researchers described the case of a South African woman whose VP diagnosis was delayed as a result of her unusual symptoms and the inability of doctors to perform standard diagnostic tests.
She sought medical care for pain in her abdomen, right arm, and back. She had several pre-existing conditions, including chronic kidney disease and a diagnosis of cutaneous porphyria, a form of porphyria that primarily affects the skin.
After a series of tests, clinicians detected the presence of methicillin-sensitive Staphylococcus aureus (MSSA), a bacteria that can cause staph infections. The woman was given antibiotic treatment, but the infection led to sepsis, an extreme and potentially life-threatening reaction to an infection.
On her fourth day in the hospital, the woman’s organs began to progressively shut down, which the clinical team attributed to her MSSA sepsis. In particular, they noted worsening kidney failure leading to anuria. With more antibiotics and continuous renal replacement therapy (CRRT), a type of treatment used to filter blood and balance fluid levels when the kidneys are unable to do so, her symptoms began to ease.
However, after nine days in the hospital, the woman began showing neurological symptoms, including limb weakness, involuntary facial movements, and reduced reflexes in her arms and legs.
“Her neurological presentation was atypical for resolving MSSA sepsis; therefore, alternative diagnoses, including an acute porphyric attack, were explored,” the researchers wrote.
Variegate porphyria diagnosis delayed
Clinicians attempted to measure PBG levels in the woman’s urine samples collected before the onset of anuria, but the samples had been exposed to light, which can degrade PBG and cause its levels to be falsely lowered. In this case, urine tests came back negative for the presence of PBG. Blood tests also proved inconclusive, with interpretation complicated by the woman’s infection and multiorgan failure. Fecal testing can also be used to diagnose VP, but was not available in the hospital.
Without a clear diagnosis, the team examined the fluid that had been removed from the woman during CRRT, called effluent. Compared with PBG levels measured in the effluent of another patient who did not have porphyria, the woman’s effluent had very high PBG levels, consistent with an acute VP attack.
Clinicians then started her on therapies typically used for acute porphyria attacks, including the administration of carbohydrates to reduce the production of porphyrins and their precursors. They also kept her on CRRT and began therapeutic plasma exchange, a treatment used to remove and replace plasma (the blood’s liquid portion).
Despite these aggressive therapies, the woman’s neurological symptoms continued to worsen and her family transferred her to palliative care. After 33 days in the hospital, she died.
“Progressive neurological sequelae and multiorgan failure that arise in the absence of a clear etiology [cause] should prompt the early consideration of an underlying acute porphyric crisis as a diagnosis of exclusion,” the researchers wrote.
They also noted that “in patients with anuric renal failure requiring renal replacement therapy, effluent porphyrin assays can serve as an adjunctive diagnostic tool to confirm the presence of an acute porphyric attack.
“Further research is needed to establish clear effluent reference ranges for PBGs that constitute an acute porphyric crisis in VP and other acute porphyrias,” they added.
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