Complex symptoms may point to rare disease, case study shows
Man with MGUS and unexplained symptoms diagnosed with variegate porphyria
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A man with monoclonal gammopathy of undetermined significance (MGUS), a blood abnormality that increases the risk of blood cancer, was later also diagnosed with variegate porphyria after developing widespread, unexplained symptoms.
The case highlights the importance of considering rare diseases when a group of symptoms suddenly appear together and cannot be explained by the current diagnosis alone, researchers said in a report detailing the diagnostic process.
The man’s symptoms were successfully controlled with Givlaari (givosiran), demonstrating how the treatment can manage porphyria symptoms when standard treatment with hemin is unsuccessful or cannot be used, they said.
The international team of researchers described the case in a study, “Neurovisceral Syndrome in a Patient with Monoclonal Gammopathy of Undetermined Significance: A Confirmed Case of Variegate Porphyria,” published in Cureus.
Variegate porphyria is a type of acute hepatic porphyria caused by mutations in the PPOX gene, which encodes the enzyme protoporphyrinogen oxidase. This enzyme is involved in the production of heme, and when it does not work properly, it causes symptoms that can differ widely from one patient to another.
Symptom overlap can pose complications
“This broad symptom range can make identifying a single underlying cause difficult and delay timely diagnosis,” in part because of possible overlap with other diseases, the researchers wrote. “This overlap is clinically important, as it can obscure the presentation and complicate the diagnostic pathway in patients with suspected porphyria.”
The 53-year-old man was admitted to the hospital for depression. During his stay, he developed red, blistering skin on his chest and arms, and his face would flush. Doctors initially suspected an infection or an allergic reaction and treated the man with antibiotics and creams. But his symptoms continued to worsen.
After several hospital visits and tests, the man was diagnosed with MGUS, a condition in which immune cells called plasma cells produce an abnormally high level of the M protein. While patients are at an increased risk of blood cancer, specifically multiple myeloma, MGUS is benign and usually does not cause symptoms. This made the case even more confusing.
The man had a history of diabetes, high blood pressure, and heart disease. He also smoked and occasionally drank alcohol. Over the next three months, he had episodes of stomach and chest pain, mood changes, tiredness, shaking, brain fog, nerve pain in his hands, dizziness when standing, and gradual weight loss.
Doctors collected his urine over 24 hours and found high porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), both of which accumulate to toxic levels in variegate porphyria. While genetic testing could have confirmed a diagnosis, it was not available, and the diagnosis was based on the man’s symptoms and the results of the urine test.
Initially, the man was treated with intravenous (into-the-vein) hemin, which helps reduce toxic substances such as PBG and ALA by slowing down the body’s production of heme. However, he developed thrombophlebitis, a painful vein inflammation, forcing doctors to stop treatment. Because he could not tolerate hemin, doctors switched him to Givlaari.
Gilvaari, approved for acute hepatic porphyria, targets the genetic cause of porphyria by reducing the production of an enzyme involved in an early step of heme production in the liver. This prevents the accumulation of the toxic substances that cause variegate porphyria symptoms.
After starting the subcutaneous (under-the-skin) injections of Givlaari, the man’s symptoms eased. His blisters healed, his nerve pain decreased, his mood and concentration returned to normal, and he no longer experienced abdominal or chest pain.
The man’s condition remained stable over three months of follow-up, with no new symptoms. His overall quality of life improved, and he resumed daily activities. His MGUS was not treated directly, since it was not causing any symptoms. Instead, it was carefully monitored with regular check-ups for blood cancer.
“The patient is alive and clinically stable at the time of reporting,” the researchers wrote. “This case demonstrates how different diseases can mimic acute hepatic porphyrias and why an understanding of the neuropsychiatric and dermatological patterns of [variegate porphyria] is necessary to reach an accurate diagnosis in complex situations.”
