ArticleAnnals of hematology2021
Severe homocysteinemia in two givosiran-treated porphyria patients: is free heme deficiency the culprit?
Article in Annals of hematology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study.Liver international : official journal of the International Association for the Study of the Liver · 2022Trial
- Real-World Experience With Givosiran in Acute Porphyrias: A Narrative Review and a Novel Hypothesis.Cureus · 2026Review
- Porphyrias: Pathophysiology and clinical management recommendations for hepatologists.Hepatology communications · 2025Review
- Baseline urinary ALA and PBG as criteria for starting pharmacologic prophylactic treatment in acute intermittent porphyria treated with givosiran.Molecular genetics and metabolism reports · 2024Article
- Elevated homocysteine is negatively correlated with plasma cystathionine β-synthase activity in givosiran-treated patients.JIMD reports · 2024Article
- Preventing hyperhomocysteinemia using vitamin BMolecular genetics and metabolism reports · 2024Article
- Recurrent symptoms of acute intermittent porphyria after biochemical normalization with givosiran-An ongoing clinical conundrum.JIMD reports · 2023Article
- Idiosyncratic drug-induced liver injury caused by givosiran in a patient with acute intermittent porphyria.Molecular genetics and metabolism reports · 2023Article
- Iron Metabolism in the Disorders of Heme Biosynthesis.Metabolites · 2022Review
- Therapy Follows Diagnosis: Old and New Approaches for the Treatment of Acute Porphyrias, What We Know and What We Should Know.Diagnostics (Basel, Switzerland) · 2022Review
- Endothelial Dysfunction in Acute Hepatic Porphyrias.Diagnostics (Basel, Switzerland) · 2022Article
- Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives.Orphanet journal of rare diseases · 2022Review
- Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics.International journal of molecular sciences · 2022Article
- Spotlight on Givosiran as a Treatment Option for Adults with Acute Hepatic Porphyria: Design, Development, and Place in Therapy.Drug design, development and therapy · 2022Review
- Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications.Diagnostics (Basel, Switzerland) · 2021Review
- Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias.Diagnostics (Basel, Switzerland) · 2021Review
- Porphyrias in the Age of Targeted Therapies.Diagnostics (Basel, Switzerland) · 2021Review
- Multiple roles of haem in cystathionine β-synthase activity: implications for hemin and other therapies of acute hepatic porphyria.Bioscience reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Givosiran is a novel approach to treat patients with acute intermittent porphyrias (AIP) by silencing of ∂-ALA-synthase 1, the first enzyme of heme biosynthesis in the liver. We included two patients in the Envision study who responded clinically well to this treatment. However, in both patients, therapy had to be discontinued because of severe adverse effects: One patient (A) developed local injection reactions which continued to spread all over her body with increasing number of injections and eventually caused a severe systemic allergic reaction. Patient B was hospitalized because of a fulminant pancreatitis. Searching for possible causes, we also measured the patients plasma homocysteine (Hcy) levels in fluoride-containing collection tubes: by LC-MS/MS unexpectedly, plasma Hcy levels were 100 and 200 in patient A and between 100 and 400 μmol/l in patient B. Searching for germline mutations in 10 genes that are relevant for homocysteine metabolism only revealed hetero- and homozygous polymorphisms in the MTHFR gene. Alternatively, an acquired inhibition of cystathionine-beta-synthase which is important for homocysteine metabolism could explain the plasma homocysteine increase. This enzyme is heme-dependent: when we gave heme arginate to our patients, Hcy levels rapidly dropped. Hence, we conclude that inhibition of ∂-ALA-synthase 1 by givosiran causes a drop of free heme in the hepatocyte and therefore the excessive increase of plasma homocysteine. Hyperhomocysteinemia may contribute to the adverse effects seen in givosiran-treated patients which may be due to protein-N-homocysteinylation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.