Health impact of acute intermittent porphyria in latent and non-recurrent attacks patients

Abstract

Background Acute intermittent porphyria (AIP) is a genetic disease characterized by acute neurovisceral attacks. Long-term clinical conditions, chronic symptoms and impaired health related quality of life (HRQoL) have been reported during non-attack periods but mainly in patients with recurrent attacks. Our aim was to investigate these aspects in sporadic AIP (SA-AIP) and latent AIP (L-AIP) patients. Fifty-five participants, 27 SA-AIP (< 4 attacks/year) and 28 L-AIP patients with a prevalent founder mutation from Spain were included. Medical records were reviewed, and individual interviews, physical examinations, biochemical analyses, and abdominal ultrasound scans were conducted. HRQoL was assessed through an EQ-5D-5L questionnaire. A comparative study was made between SA-AIP and L-AIP patients. Results The earliest long-term clinical condition associated with SA-AIP was chronic kidney disease. Chronic symptoms were reported in 85.2 % of SA-AIP and 46.4 % of L-AIP patients. Unspecific abdominal pain, fatigue, muscle pain and insomnia were significantly more frequent in SA-AIP than in L-AIP patients. The EQ-5D-5L index was lower in SA-AIP (0.809 vs. 0.926, p = 0.0497), and the impact of “pain”, “anxiety-depression” and “mobility” was more intense in the EQ-5D-5L domains in SA-AIP than in L-AIP subjects and the general Spanish population. Conclusions AIP remains a chronically symptomatic disease that adversely affects health and quality of life, even in patients with low rate of acute attacks. We suggest a regular monitoring of patients with symptomatic AIP regardless of their attack rate or the time since their last attack, with proper pain management and careful attention to kidney function.

Acute Hepatic Porphyria: Pathophysiological Basis of Neuromuscular Manifestations

“…Acute flaccid paralysis presenting as acute to subacute symmetric proximal quadriparesis due to motor axonal polyradiculopathy or neuronopathy represents the most common neuromuscular presentation of AHP in the Emergency Department and Intensive Care Unit (ICU), resembling clinical and neurophysiological features of Guillain–Barré syndrome and representing one of the main factors for medical and financial burden of AHP ( Albers and Fink, 2004 ; Wu et al, 2015 ; Neeleman et al, 2018 ; Suh et al, 2019 ; Buendía-Martínez et al, 2021 ).…”

“…Chronic fatigue represents one of the most important chronic symptoms in AHP leading to decreased quality of life, mainly in patients with recurrent life-threatening acute neurovisceral attacks ( Naik et al, 2016 ; Gouya et al, 2020 ). However, oligosymptomatic and non-recurrent attack patients may present with chronic fatigue, possibly not associated with previous muscle or nerve toxic damage mechanisms ( Buendía-Martínez et al, 2021 ). Porphyrins are considered to have a possible key role involved in several fatigue syndromes; however a well-defined mechanism related to fatigue pathogenesis in AHP is still unknown ( Downey, 1994 ).…”

“…Porphyrins are considered to have a possible key role involved in several fatigue syndromes; however a well-defined mechanism related to fatigue pathogenesis in AHP is still unknown ( Downey, 1994 ). It is unknown if the previously discussed mechanisms involving mitochondrial dysfunction, abnormal hemoprotein compound formation, and direct muscle injury may play any role in its pathogenesis ( Lin et al, 2011 ; Wissbrock et al, 2019 ; Buendía-Martínez et al, 2021 ). There is also a large discussion regarding the possible role of chronic neuropathic painful symptoms and chronic or recurrent sleep disturbances in the emergence of chronic fatigue, so that both affects up to 15% of all AHP patients at the late stages of a disease course ( Gouya et al, 2020 ; Souza et al, 2021 ).…”

Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy

“…AHP has been associated with the long-term complications such as hypertension, chronic kidney disease and liver cancer [ 6 , 23 , 25 ]. A few patients have developed chronic neuropathy and encephalopathy after recurrent attacks [ 13 , 15 , 26 , 27 ].…”

Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications

“…While givosiran has represented a breakthrough in the management of acute porphyrias, it must not be overlooked that, other than acute attacks, patients with AHPs develop long-term complications such as chronic neuropathy, hepatocellular carcinoma, and chronic kidney disease (CKD) [ 13 , 14 ]. In fact, porphyria-associated kidney disease (PAKD) has been recognized as a distinct entity with specific pathological and clinical features [ 15 ], for instance, most patients with AIP suffer a progressive impairment of kidney function, with an estimated decline in glomerular filtration rate (eGFR) of 1 mL/min per 1.73 m 2 per year [ 16 ].…”