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Acta Clin Belg 2021 May 3:1-7. Epub 2021 May 3.

Department of General Internal Medicine, KU Leuven, Leuven, Belgium.

Porphyrias are disorders of the haem biosynthesis which are encountered infrequently and which often present themselves atypically as a combination of gastrointestinal, neurologic and/or dermatologic symptoms. Although they are primarily caused by enzyme defects, inheritance patterns are mostly not evident. Considering all of these characteristics, it is not surprising that there is a long delay between the onset of symptoms and the diagnosis of the disease, with as possible consequences impaired quality of life, irreversible neurologic damage and even death. Read More

Drugs 2021 Apr 19. Epub 2021 Apr 19.

Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.

Givosiran (Givlaari) is an δ-aminolevulinic acid synthase 1 (ALAS1)-directed small interfering RNA (siRNA) approved for the treatment of acute hepatic porphyria (AHP). In the phase 3 ENVISION trial, givosiran significantly reduced the annualized rate of composite porphyria attacks (i.e. Read More

J Inherit Metab Dis 2021 Apr 16. Epub 2021 Apr 16.

Norwegian Porphyria Centre (NAPOS), Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long-term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease-states. Read More

Biomedicines 2021 Mar 5;9(3). Epub 2021 Mar 5.

Hepatology Program, Cima Universidad de Navarra, 31008 Pamplona, Spain.

Acute porphyria attacks are associated with the strong up-regulation of hepatic heme synthesis and over-production of neurotoxic heme precursors. First-line therapy is based on carbohydrate loading. However, altered glucose homeostasis could affect its efficacy. Read More

Mol Genet Genomic Med 2021 Mar 25:e1059. Epub 2021 Mar 25.

Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Hospital de Clínicas José de San Martín, CONICET-UBA, Buenos Aires, Argentina.

Background: Acute Hepatic Porphyrias (AHPs) are characterized by an acute neuroabdominal syndrome including both neuropsychiatric symptoms and neurodegenerative changes. Two main hypotheses explain the pathogenesis of nervous system dysfunction: (a) the ROS generation by autooxidation of 5-aminolevulinic acid accumulated in liver and brain; (b) liver heme deficiency and in neural tissues that generate an oxidative status, a component of the neurodegenerative process.

Methods: We review results obtained from Acute Intermittent Porphyria (AIP) and Variegate Porphyria (VP) families studied at clinical, biochemical, and molecular level at the CIPYP in Argentina. Read More

iScience 2021 Mar 6;24(3):102152. Epub 2021 Feb 6.

Department of Chemistry, University of Eastern Finland, 80130 Joensuu, Finland.

Porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis, catalyzes the sequential coupling of four porphobilinogen (PBG) molecules into a heme precursor. Mutations in PBGD are associated with acute intermittent porphyria (AIP), a rare metabolic disorder. We used Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to demonstrate that wild-type PBGD and AIP-associated mutant R167W both existed as holoenzymes (E) covalently attached to the dipyrromethane cofactor, and three intermediate complexes, ES, ES, and ES, where S represents PBG. Read More

Arq Neuropsiquiatr 2021 01;79(1):68-80

Universidade Federal de São Paulo, Department of Neurology and Neurosurgery, Division of Neuromuscular Diseases, São Paulo SP, Brazil.

Background: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis.

Objective: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias.

Methods: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Read More

Orphanet J Rare Dis 2021 02 27;16(1):106. Epub 2021 Feb 27.

Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.

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. Read More

Ann Indian Acad Neurol 2020 Sep-Oct;23(5):711-712. Epub 2020 Dec 8.

Department of General Medicine, M.E.S. Medical College, Perinthalmanna, Kerala, India.

Drugs Today (Barc) 2021 Jan;57(1):47-59

Section on Gastroenterology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.

Porphyrias are a family of rare diseases chiefly due to inborn errors of heme biosynthesis. The porphyrias are generally characterized either by the main site of overproduction of heme precursors (hepatic or erythropoietic) or the main clinical manifestations (acute or cutaneous). The regulation of 5- (or δ)-aminolevulinic acid synthase 1 (ALAS1) plays a key role in the pathway of normal hepatic heme synthesis, providing insight into the pathophysiologic mechanisms and potential therapeutic targets for the treatment of the porphyrias. Read More

J Neurol Sci 2021 03 31;422:117334. Epub 2021 Jan 31.

Department of Neurology, University of Regensburg, Bezirksklinikum Regensburg, Germany. Electronic address:

JIMD Rep 2021 Jan 1;57(1):85-93. Epub 2020 Oct 1.

Alnylam Pharmaceuticals Cambridge Massachusetts USA.

Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life-threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, δ-aminolevulinic acid (ALA), and porphobilinogen (PBG), which are thought to be causal for the disease manifestations. Novel therapeutic treatments such as givosiran, an RNA interference therapeutic that was recently approved for treatment of adults with AHP, are focused on reducing the levels of ALA and PBG in patients toward levels observed in a healthy population. Read More

Int J Mol Sci 2021 Jan 12;22(2). Epub 2021 Jan 12.

Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease with low clinical penetrance, caused by mutations in the hydroxymethylbilane synthase () gene, which encodes the third enzyme in the haem biosynthesis pathway. In susceptible mutation carriers, triggering factors such as hormonal changes and commonly used drugs induce an overproduction and accumulation of toxic haem precursors in the liver. Clinically, this presents as acute attacks characterised by severe abdominal pain and a wide array of neurological and psychiatric symptoms, and, in the long-term setting, the development of primary liver cancer, hypertension and kidney failure. Read More

J Int Med Res 2021 Jan;49(1):300060520983143

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disease with a broad spectrum of clinical manifestations, and can be easily confused with other diseases. Many patients with porphyria may have symptoms of peripheral nerve damage during an AIP attack, but most such patients are usually only mildly affected. Herein, we describe the case of an undiagnosed woman who developed overall weakness and respiratory failure within 48 hours, leading to her referral to the intensive care unit. Read More

Liver Transpl 2021 Apr 12;27(4):477-478. Epub 2021 Feb 12.

Department of Preventive Medicine and Population Health, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX.

Clin Case Rep 2020 Dec 30;8(12):2483-2487. Epub 2020 Jul 30.

Department of Endocrinology and Nephrology, Inflammation and Infection Karolinska University Hospital Stockholm Sweden.

In cases of recurrent attacks of acute porphyria during pregnancy, prophylactic administration of heme arginate should be considered. Clinical and biochemical monitoring of the disease and a close collaboration with a porphyria center are crucial. Read More

Neurol Res Pract 2020 20;2. Epub 2020 Jan 20.

Department of Neurology, Klinikum Würzburg Mitte gGmbH, Standort Juliusspital, 97070 Würzburg, Germany.

We present the case of an 18 year old Caucasian with known celiac disease, who suffered a severe first attack of acute intermittent porphyria (AIP) with neuropsychiatric symptoms, severe tetraparesis and respiratory insufficiency. Treatment with heme arginate and high-dose intravenous glucose and rigorous rehabilitation resulted in a slow but almost complete recovery of her motor symptoms. To our knowledge this is the first case of acute intermittent porphyria triggered by malnutrition in the context of celiac disease. Read More

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):400-410

University of Washington, Seattle, Washington.

The porphyrias are a family of metabolic disorders caused by defects in the activity of one of the enzymes in the heme biosynthetic pathway. Acute intermittent porphyria (AIP), caused by autosomal dominant mutations in the gene encoding hydroxymethylbilane synthase, can lead to hepatocyte overaccumulation and systemic distribution of the proximal porphyrin precursors, 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA and PBG are toxic to neurons and extrahepatic tissue and cause the neurovisceral clinical manifestations of AIP. Read More

Liver Transpl 2021 Apr 29;27(4):491-501. Epub 2021 Jan 29.

Hepatology Division, Department of Upper GI Diseases, Porphyria Centre Sweden, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Read More

Med Hypotheses 2020 Nov 3;144:110242. Epub 2020 Sep 3.

Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, A. Vésale Hospital, Université Libre de Bruxelles, Montigny-le-Tilleul, Belgium.

The outbreak of coronavirus disease 2019 (COVID-19) requires urgent need for effective treatment. Severe COVID-19 is characterized by a cytokine storm syndrome with subsequent multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS), which may lead to intensive care unit and increased risk of death. While awaiting a vaccine, targeting COVID-19-induced cytokine storm syndrome appears currently as the efficient strategy to reduce the mortality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Read More

Am J Case Rep 2020 Nov 18;21:e927832. Epub 2020 Nov 18.

School of Medicine, Universidade Catolica de Brasilia, Brasilia, Brazil.

BACKGROUND Acute intermittent porphyria is an inherited disease caused by a defect in heme biosynthesis, with accumulation of neurotoxic metabolites leading to acute neurovisceral symptoms. Some patients develop long-term neurological and renal damage after the acute episodes, many of them requiring hemodialysis. Since heme production in the human body occurs predominantly in the bone marrow and liver, liver transplantation has been shown to significantly reduce the production of neurotoxic metabolites, effectively controlling the disease. Read More

N Engl J Med 2020 11;383(20):1989-1990

Université Paris Diderot, Paris, France.

N Engl J Med 2020 11;383(20):1989

Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

Intractable Rare Dis Res 2020 Nov;9(4):205-216

Department of Endocrinology, The second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by mutations in porphobilinogen deaminase (PBGD), the third enzyme of the heme synthesis pathway. Symptoms of AIP usually manifest as intermittent acute attacks with occasional neuropsychiatric crises. The management of AIP includes treatment of acute attacks, prevention of attacks, long-term monitoring and treatment of chronic complications. Read More

Intractable Rare Dis Res 2020 Nov;9(4):196-204

Department of Endocrinology, The second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Acute intermittent porphyria (AIP) is a dominant inherited disorder with a low penetrance that is caused by mutations in the gene coding for hydroxymethylbilane synthase (HMBS). Information about the epidemiology and molecular genetic features of this rare disorder is crucial to clinical research, and particularly to the evaluation of new treatments. Variations in the prevalence and penetrance of AIP in various studies may due to the different inclusion criteria and methods of assessment. Read More

Intractable Rare Dis Res 2020 Nov;9(4):187-195

Department of Endocrinology, The second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Porphyrias are a group of inherited metabolic diseases that include eight types, each of which is caused by a mutation that affects an enzyme of the heme biosynthetic pathway. When an enzyme defect has physiological significance, it leads to overproduction of pathway precursors prior to the defective step. The partial absence of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD) also known as hydroxymethylbilane synthase (HMBS), results in acute intermittent porphyria (AIP), which affects mainly women. Read More

Case Rep Genet 2020 15;2020:8873219. Epub 2020 Oct 15.

Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP)-CONICET, Hospital de Clínicas-UBA, Buenos Aires, Argentina.

Porphyrias are a heterogeneous group of metabolic disorders that result from the altered activity of specific enzymes of the heme biosynthetic pathway and are characterized by accumulation of pathway intermediates. Porphyria cutanea tarda (PCT) is the most common porphyria and is due to deficient activity of uroporphyrinogen decarboxylase (UROD). Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias, caused by decreased activity of hydroxymethylbilane synthase (HMBS). Read More

J Med Econ 2020 Dec 27;23(12):1441-1449. Epub 2020 Oct 27.

Wake Forest Baptist Health, Winston-Salem, NC, USA.

Objective: Since 1983, hemin has been FDA-approved for acute intermittent porphyria (AIP) attacks. In 2019, FDA approved givosiran for the treatment of adults with acute hepatic porphyria. The objective of this research was to estimate and compare the total cost of AIP-related healthcare for patients treated with hemin or givosiran. Read More

Indian J Crit Care Med 2020 Aug;24(8):724-726

Department of Radiodiagnosis, AIG Hospitals, Hyderabad, Telangana, India.

Acute intermittent porphyria (AIP) is an acute neurovisceral porphyria caused due to inherited deficiency of porphobilinogen deaminase (also called hydroxymethylbilane synthase) (HMBS) in the heme biosynthesis pathway. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES), which is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral edema, headaches, nausea, and seizures. AIP should be considered when a patient presents with unexplained abdominal pain and seizures. Read More

Cir Esp 2020 Oct 2. Epub 2020 Oct 2.

Unidad de Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital General Universitario de Alicante, Alicante, España; Instituto de Investigación Sanitaria y Biomédica de Alicante -ISABIAL-, Alicante, España.