Preventive porphyria treatment aids man’s recovery after severe attacks
Case highlights possible 'catastrophic' outcomes of delayed diagnosis
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Long-term treatment with Givlaari (givosiran), an approved medication for acute intermittent porphyria (AIP), helped prevent further episodes of AIP in a man in his 20s with severe neurological complications from earlier attacks, according to a case study.
The researchers say using the injection medication as a preventive treatment potentially facilitated the man’s recovery — and helped him regain daily function — after a delayed initial identification of his porphyria.
Following severe first attacks of AIP — a diagnosis that was reached about two weeks after his initial symptoms — the man had difficulty breathing and couldn’t use his arms or legs. Ultimately, with a year of Givlaari treatment, he had no further attacks and made substantial gains in motor and respiratory function, the researchers reported.
“Overall, this case exemplifies how delayed recognition of AIP can lead to catastrophic neurological outcomes, while timely biochemical diagnosis and access to disease-modifying therapy can substantially alter the disease course,” the researchers wrote, noting that the man had “rapidly progressive” symptoms.
The study, “Advanced Management of Acute Intermittent Porphyria: The Role of Givosiran Therapy in Improving Long-Term Outcomes-A Case Study,” was published in the journal Clinical Case Reports.
Porphyria refers to a group of genetic diseases caused by mutations that affect the production of the molecule heme, a part of the hemoglobin protein in red blood cells that transports oxygen. As a result, precursor molecules to heme build up in the body, reaching toxic levels.
AIP is a form of the condition characterized by the accumulation of two heme precursors: porphobilinogen, or PBG, and aminolevulinic acid, called ALA. Their buildup can lead to sudden neurovisceral crises, which are marked by severe abdominal pain, problems with involuntary bodily functions such as heart rate and blood pressure, neuropsychiatric symptoms, and progressive motor function decline.
Man, 28, developed AIP after vehicle accident
Sometimes, an infection, injury, or environmental exposure triggers a bout of AIP in someone who was previously healthy — which was the case here, the researchers noted.
Short-term treatment generally involves intravenous, or into-the-vein, administration of glucose (blood sugar), which can help prevent further toxic porphyrin buildup. If this isn’t successful, intravenous hemin, a molecule related to heme, can help ease symptoms.
Once a patient is stable, doctors may recommend long-term treatment with Givlaari to help prevent further attacks. Administered through a subcutaneous, or under-the-skin, injection once a month, Givlaari works by reducing the levels of aminolevulinate synthase 1, an enzyme that causes ALA and PBG levels to rise.
The researchers noted that “early recognition of acute intermittent porphyria is critical to prevent irreversible neurological damage.” Still, diagnostic delays can occur, particularly in the context of broader health events that may obscure the underlying condition.
That’s what occurred in this case, involving a previously healthy 28-year-old man in Brazil. Three days after sustaining mild injuries in a motor vehicle accident, he began to experience abdominal pain, constipation, nausea, and vomiting that were resistant to standard medications.
Over the following days, the cause remained unclear. Ten days after his first symptoms, the man had a seizure and was admitted to a specialist care center for further evaluation. He had high blood pressure, a fast heart rate, unusually dark urine, and an altered mental state.
Based on this array of symptoms, the care team suspected AIP.
Treatment with Givlaari followed hospital discharge
That diagnosis was confirmed 12 days after the onset of symptoms, with the results of a urine test that measured PBG and ALA levels: The man’s were higher than normal.
Clinicians initially treated him with intravenous glucose, but his neurological condition continued to deteriorate. He became unable to move any of his limbs, had sensory problems, and developed respiratory failure that needed invasive mechanical ventilation.
Intravenous hemin was started 25 days after his diagnosis. Although the man initially showed some positive response, he later began to worsen again, potentially due to an infection. With a second round of hemin treatment, he gradually stabilized.
Over a total of five months in the hospital, the man’s mobility improved, and he was able to reduce his reliance on ventilation. Still, his PBG levels remained abnormally high.
After his discharge, he started prophylaxis, or preventive treatment, with Givlaari, the researchers reported.
One year later, he had not experienced any further AIP attacks and showed substantial neurological improvement, regaining the ability to walk with assistance. His PBG levels remained elevated, however.
In severe cases … long-term treatment with [Givlaari] may allow significant functional recovery and prevent recurrence.
According to the researchers, this case illustrates how Givlaari can help facilitate recovery even in complex cases of AIP.
“In severe cases with advanced [nerve damage] and respiratory failure, long-term treatment with [Givlaari] may allow significant functional recovery and prevent recurrence, even in the presence of persistent biochemical abnormalities,” the researchers wrote.
During follow-up, the man underwent genetic testing to identify the specific mutation that caused his condition. His mother was found to carry the same mutation, and she received medical advice about how to avoid events that could trigger an AIP attack.
“The integration of rapid qualitative screening, confirmatory quantitative testing, acute hemin therapy, and long-term prophylaxis with [Givlaari] represents a comprehensive approach capable of improving both survival and long-term functional prognosis in patients with severe AIP,” the researchers concluded.
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