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Frontiers in Neurology 2024Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and...
BACKGROUND
Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP.
METHODS
We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN).
RESULTS
During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy.
CONCLUSION
This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.
PubMed: 38715693
DOI: 10.3389/fneur.2024.1384678 -
European Review For Medical and... Apr 2024We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering...
BACKGROUND
We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks' recurrence.
CASE REPORT
A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly). Serial neurological, structural, and resting-state functional magnetic resonance imaging (MRI) evaluations were performed, including clinical scales and neurophysiological tests. Delta-aminolevulinic acid urinary levels dropped drastically during treatment. In parallel, all the administered neurological rating scales and neurophysiological assessments showed improvement in all domains. Moreover, an improvement in central motor conduction parameters and resting-state functional connectivity in the sensory-motor network was noticed. At the end of the follow-up, the patient could walk unaided after using a wheelchair for 5 years.
CONCLUSIONS
A clear beneficial effect of givosiran was demonstrated in our patient with both clinical and peripheral nerve neurophysiologic outcome measures. Moreover, we first reported a potential role of givosiran in recovering central motor network impairment in acute intermittent porphyria (AIP), which was previously unknown. This study provides Class IV evidence that givosiran improves chronic porphyric neuropathy.
Topics: Humans; Male; Porphyria, Acute Intermittent; Child; Acetylgalactosamine; Aminolevulinic Acid; Magnetic Resonance Imaging; Pyrrolidines; Uridine; Recovery of Function; Chronic Disease; Treatment Outcome
PubMed: 38708485
DOI: 10.26355/eurrev_202404_36055 -
Cureus Apr 2024Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for...
Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for diagnosing pseudoporphyria. It has an unknown underlying pathophysiology with a normal or near-normal porphyrin profile. Pseudoporphyria has been associated with chronic renal failure and hemodialysis, medications, and tanning beds. In drug-induced pseudoporphyria cases, eliminating the suspected photosensitizing drug improves the disease typically within weeks to months (on average eight weeks). In genetically predisposed individuals, phototoxic metabolites may trigger the development of skin fragility, bullae, milia, and scarring on the dorsum of the hands and other sun-exposed areas. Wearing a broad-spectrum sunscreen and maintaining strict ultraviolet protection is essential in cases of pseudoporphyria. We report the case of a 20-year-old male who presented to us with complaints of photosensitivity and multiple erosions with irregular scars over photo-exposed areas involving the dorsum of the hands and face predominantly. The patient was evaluated further to determine the underlying cause. A wood's lamp examination of the urine was done, which did not show fluorescence. Based on clinical and laboratory findings, the diagnosis of pseudoporphyria was made, and the patient was started on the oral antimalarial agent hydroxychloroquine sulfate with strict sun protection.
PubMed: 38707054
DOI: 10.7759/cureus.57574 -
The New Zealand Medical Journal May 2024
Topics: Humans; Female; Preimplantation Diagnosis; Pregnancy; Adult; Embryo Transfer
PubMed: 38696836
DOI: 10.26635/6965.6403 -
ACG Case Reports Journal May 2024Porphyria caused by inherited disorders in heme biosynthesis can lead to accumulation of porphyrins in various organs. Liver involvement due to porphyria mostly results...
Porphyria caused by inherited disorders in heme biosynthesis can lead to accumulation of porphyrins in various organs. Liver involvement due to porphyria mostly results in cholestasis leading to liver cirrhosis or hepatocellular carcinoma. Congenital erythropoietic porphyria (CEP), a rare porphyria due to deficiency of uroporphyrinogen III synthase, mostly results in cutaneous manifestations. There are reports of liver involvement including varying degree of fibrosis in patients with CEP. We report a unique case of a patient with CEP who developed porto-sinusoidal vascular disease with complications of portal hypertension that necessitated liver transplantation.
PubMed: 38682079
DOI: 10.14309/crj.0000000000001336 -
Biomedicines Apr 2024Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being... (Review)
Review
BACKGROUND
Hemin is clinically used in acute attacks of porphyria; however, recent evidence has also highlighted its capability to stimulate the heme oxygenase enzyme, being associated with cytoprotective, antioxidant, and anti-inflammatory effects. Indeed, current preclinical evidence emphasizes the potential anti-inflammatory role of hemin through its use in animal models of disease. Nevertheless, there is no consensus about the underlying mechanism(s) and the most optimal therapeutic regimens. Therefore, this review aims to summarize, analyze, and discuss the current preclinical evidence concerning the pharmacological effect of hemin.
METHODS
Following the application of the search expression and the retrieval of the articles, only nonclinical studies in vivo written in English were considered, where the potential anti-inflammatory effect of hemin was evaluated.
RESULTS
Forty-nine articles were included according to the eligibility criteria established. The results obtained show the preference of using 30 to 50 mg/kg of hemin, administered intraperitoneally, in both acute and chronic contexts. This drug demonstrates significant anti-inflammatory and antioxidant activities considering its capacity for reducing the expression of proinflammatory and oxidative markers.
CONCLUSIONS
This review highlighted the significant anti-inflammatory and antioxidant effects of hemin, providing a clearer vision for the medical community about the use of this drug in several human diseases.
PubMed: 38672251
DOI: 10.3390/biomedicines12040898 -
Biomedicines Mar 2024Monitoring antibiotic retention in human body fluids after treatment and controlling heavy metal content in water are important requirements for a healthy society....
Monitoring antibiotic retention in human body fluids after treatment and controlling heavy metal content in water are important requirements for a healthy society. Therefore, the approach proposed in this study is based on developing new optical sensors using porphyrin or its bifunctional hybrid materials made with AuNPs to accomplish the accurate detection of chloramphenicol and cobalt. To produce the new optical chloramphenicol sensors, 2,7,12,17-tetra-tert-butyl-5,10,15,20-tetraaza-21H,23H-porphine (TBAP) was used, both alone in an acid medium and as a hybrid material with AuNPs in a water-DMSO acidified environment. The same hybrid material in the unchanged water-DMSO medium was the sensing material used for Co monitoring. The best results of the hybrid materials were explained by the synergistic effects between the TBAP azaporphyrin and AuNPs. Chloramphenicol was accurately detected in the range of concentrations between 3.58 × 10 M and 3.37 × 10 M, and the same hybrid material quantified Co in the concentration range of 8.92 × 10 M-1.77 × 10 M. In addition, we proved that AuNPs can be used for the detection of azaporphyrin (from 2.66 × 10 M to 3.29 × 10 M), making them a useful tool to monitor porphyrin retention after cancer imaging procedures or in porphyria disease. In conclusion, we harnessed the multifunctionality of this azaporphyrin and of its newly obtained AuNP plasmonic hybrids to detect chloramphenicol and Co quickly, simply, and with high precision.
PubMed: 38672126
DOI: 10.3390/biomedicines12040770 -
International Journal of Dermatology Apr 2024Despite its rarity, porphyria cutanea tarda (PCT) is globally recognized as the most common form of cutaneous porphyria. This study aims to review the underlying...
BACKGROUND
Despite its rarity, porphyria cutanea tarda (PCT) is globally recognized as the most common form of cutaneous porphyria. This study aims to review the underlying associations and treatment of PCT in Scotland.
METHODS
We retrospectively reviewed data on 27 patients diagnosed with PCT between 1987 and 2022 at the Scottish Cutaneous Porphyria Service.
RESULTS
Males slightly predominated (66.7%). The mean ± standard deviation (SD) age at diagnosis was 55.6 ± 12.5 years. Common associated factors were heavy alcohol intake (88.5%), genetic hemochromatosis (72%), smoking (45.5%), and hepatitis C virus infection (16%). Most had multiple associated factors (70.4%). Patients with genetic hemochromatosis with the C282Y genotype exhibited higher median transferrin saturation (69.5 vs. 35, P = 0.004) and ferritin levels (observed in males only) (1175 vs. 339; P = 0.014) than those with the H636D genotype. Most (52%) received combination therapy of venesection and antimalarials, followed by venesection monotherapy (32%) and antimalarial monotherapy (16%). Overall, 95.2% achieved biochemical improvement. Median time to improvement was 7, 5, and 9 months with venesection, antimalarial, and combined treatments, respectively (P = 0.173). Biochemical remission was achieved in 50% of patients. Remission occurred in 2/4 of patients with antimalarial monotherapy (median time 19 months) and 9/13 patients with combined treatment (median time 26 months). Biochemical relapse was found in three patients, all of whom received combination therapy.
CONCLUSION
Excess alcohol intake and genetic hemochromatosis were the most common underlying associations with PCT in our Scottish cohort. Treatment for PCT should be individualized, and long-term follow-up is needed to monitor for disease relapse.
PubMed: 38647187
DOI: 10.1111/ijd.17205 -
Revista Clinica Espanola May 2024Acute hepatic porphyrias (AHPs) are a group of rare diseases that encompasses acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and...
BACKGROUND
Acute hepatic porphyrias (AHPs) are a group of rare diseases that encompasses acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolaevulinic acid dehydratase deficiency porphyria. Symptoms of AHP are nonspecific which, together with its low prevalence, difficult the diagnosis and follow-up of these patients.
MATERIAL AND METHODS
This project used DELPHI methodology to answer PICO questions related to management of patients with AHPs. The objective was to reach a consensus among multidisciplinary porhyria experts providing answers to those PICO questions for improving diagnosis and follow-up of patients with AHP.
RESULTS
Ten PICO questions were defined and grouped in four domains: 1. Biochemical diagnosis of patients with AHP. 2. Molecular tests for patients with AHP. 3. Follow-up of patients with AHP. 4. Screening for long-term complications of patients with AHP.
CONCLUSIONS
PICO questions and DELPHI methodology have provided a consensus on relevant and controversial issues for improving the management of patients with AHP.
Topics: Humans; Delphi Technique; Porphyrias, Hepatic; Quality Improvement; Consensus; Porphobilinogen Synthase
PubMed: 38642893
DOI: 10.1016/j.rceng.2024.04.010 -
Journal of Nephrology Apr 2024
PubMed: 38642240
DOI: 10.1007/s40620-023-01828-0