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J Clin Pathol 2022 May 18. Epub 2022 May 18.

Medical Biochemistry and Immunology, University Hospital of Wales Healthcare NHS Trust, Cardiff, UK.

The autosomal dominant acute hepatic porphyrias (AHPs), acute intermittent porphyria, hereditary coproporphyria (HCP) and variegate porphyria (VP), are low penetrance adult onset disorders caused by partial deficiency of enzymes of haem biosynthesis. All are associated with acute neurovisceral attacks, which are a consequence of the increased hepatic demand for haem triggered by hormones, stress, drugs or systemic infections which leads to upregulation of the pathway and overproduction of haem precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). Acute episodes are characterised by severe abdominal pain, nausea, vomiting, hyponatraemia, hypertension and tachycardia, behavioural disturbance and can progress to include seizures, peripheral motor neuropathy and posterior reversible encephalopathy syndrome if undiagnosed and untreated. Read More

Expert Rev Clin Pharmacol 2022 May 11:1-11. Epub 2022 May 11.

Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit, University of Modena and Reggio Emilia, Modena, Italy.

Introduction: Acute hepatic porphyrias (AHPs) are a family of rare inherited disorders characterized by enzyme dysfunctions in the hepatic pathway of heme biosynthesis. In AHPs, accumulation of the neurotoxic porphyrin precursors delta-aminolevulinic acid and porphobilinogen, caused by enhanced activity of hepatic aminolevulinate synthase 1 (ALAS1), is associated with acute, potentially life-threatening neurovisceral attacks. Symptoms during and between attacks dramatically reduce patients' quality of life (QoL). Read More

JIMD Rep 2022 May 18;63(3):211-215. Epub 2022 Mar 18.

Department of General Medicine Wellington Regional Hospital Wellington New Zealand.

Hereditary coproporphyria (HCP) is the rarest of the autosomal dominant acute porphyrias with an estimated incidence of 0.02 per 10 million per year. HCP has been considered to be mild in presentation compared with the more common acute intermittent porphyria although there is limited information comparing the subtypes. Read More

Mol Genet Metab Rep 2022 Mar 2;30:100842. Epub 2022 Feb 2.

Helsinki University Hospital, Department of Medicine, Finland.

Background: Acute hepatic porphyria includes four inherited disorders caused by partial deficiencies of enzymes related to the heme biosynthesis. Clinical manifestations include acute attacks, occurring mainly among female patients. This study describes the diversity of acute symptoms, changes in triggering factors and life expectancy among female patients during the past five decades. Read More

Cureus 2022 Jan 25;14(1):e21586. Epub 2022 Jan 25.

Department of Neurosurgery, University of Texas Health Science Center at San Antonio, San Antonio, USA.

Hereditary coproporphyria (HCP) is a rare disorder caused by a deficiency of an enzyme, coproporphyrinogen oxidase, in the heme synthetic pathway. This disease has a highly variable clinical presentation with acute attacks of neurologic symptoms that can last from days to months. Rarely, it and other acute porphyrias may cause ascending paralysis, which is difficult to distinguish from Guillain-Barré syndrome (GBS). Read More

J Intern Med 2022 Jun 2;291(6):824-836. Epub 2022 Mar 2.

Hepatology Division, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.

Background: The acute hepatic porphyrias (AHP) are associated with a risk of primary liver cancer (PLC), but risk estimates are unclear, and what AHP characteristics that predict PLC risk are unknown. In this register-based, matched cohort study, we assessed the PLC risk in relation to biochemical and clinical porphyria severity, genotype, age, and sex.

Methods: All patients in the Swedish porphyria register with acute intermittent porphyria (AIP), variegate porphyria (VP), or hereditary coproporphyria (HCP) during 1987-2015 were included. Read More

Diagnostics (Basel) 2021 Dec 10;11(12). Epub 2021 Dec 10.

Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Regional Reference Centre for Diagnosing and Management of Porphyrias, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico of Modena, Largo del Pozzo 71, 41124 Modena, Italy.

Porphyrias are a group of rare disorders originating from an enzyme dysfunction in the pathway of heme biosynthesis. Depending on the specific enzyme involved, porphyrias manifest under drastically different clinical pictures. The most dramatic presentation of the four congenital acute hepatic porphyrias (AHPs: acute intermittent porphyria-AIP, ALAD deficiency, hereditary coproporphyria-HCP, and porphyria variegata-VP) consists of potentially life-threatening neurovisceral attacks, for which givosiran, a novel and effective siRNA-based therapeutic, has recently been licensed. Read More

Blood Adv 2022 02;6(3):760-766

Division of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.

The Mendelian inheritance pattern of acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria is autosomal dominant, but the clinical phenotype is heterogeneous. Within the general population, penetrance is low, but among first-degree relatives of a symptomatic proband, penetrance is higher. These observations suggest that genetic factors, in addition to mutation of the specific enzyme of the biosynthetic pathway of heme, contribute to the clinical phenotype. Read More

Brain Behav 2021 11 17;11(11):e2389. Epub 2021 Oct 17.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology, Berlin, Germany.

Acute hepatic porphyrias (AHP) can cause severe neurological symptoms involving the central, autonomic, and peripheral nervous system. Due to their relative rarity and their chameleon-like presentation, delayed diagnosis and misdiagnosis are common. AHPs are genetically inherited disorders that result from heme biosynthesis enzyme deficiencies and comprise four forms: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA-dehydratase porphyria (ALADP). Read More

Acta Clin Belg 2021 Aug 7:1-7. Epub 2021 Aug 7.

Dienst Maag-Darm-Leverziekten en Metabool Centrum, UZ Leuven, Belgium.

Acute hepatic porphyrias (AHP) are a group of four different rare to ultra-rare, severely debilitating, and sometimes fatal diseases that significantly impact patients' lives: 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Based on literature estimates, a conservative estimate of the number of AHP patients in Belgium requiring treatment, defined as patients experiencing recurrent attacks and/or chronic debilitating symptoms, is likely limited to 11-34 patients. These patients face a considerable unmet need, as there is currently no pharmaceutical treatment available that effectively prevents attacks and has an impact on other chronic symptoms of the disease. Read More

Internist (Berl) 2021 Sep 29;62(9):937-951. Epub 2021 Jun 29.

Porphyrie Zentrum, Klinikum Chemnitz gGmbH, Flemmingstr. 2, 09009, Chemnitz, Deutschland.

Porphyrias are caused by enzyme defects along the heme biosynthetic pathway. The first line diagnosis of porphyria is based on specific biochemical patterns of elevated porphyrins and porphyrin precursors in urine, feces, and blood. In clinically active disease accumulated porphyrin precursors and/or porphyrins lead to abdominal, neurologic, psychiatric, endocrine and cardiovascular symptoms, liver damage and/or skin photosensitivity. Read More

Mol Genet Metab Rep 2021 Mar 13;26:100707. Epub 2021 Jan 13.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Hereditary coproporphyria (HCP) and variegate porphyria (VP) are referred to as neurocutaneous porphyrias (NCP). Data concerning their systemic presentation are limited and no direct attempt of comparison of the two has ever been made. Our aim was to describe the type and frequency of systemic manifestations of NCPs in Israeli patients. Read More

Photodermatol Photoimmunol Photomed 2021 May 20;37(3):236-242. Epub 2020 Dec 20.

Division of Dermatology, Photodermatosis Service, Rabin Medical Center, Petah Tikva, Israel.

Background: There are three major types of genetic cutaneous porphyrias (GCP): erythropoietic protoporphyria (EPP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Scarce data are available regarding their impact on patients' quality of life in the Mediterranean region.

Purpose: To describe the cutaneous features of GCP in Israel. Read More

J Dermatol Sci 2020 Nov 15;100(2):156-159. Epub 2020 Jun 15.

Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. Electronic address:

N Z Med J 2020 07 17;133(1518):81-83. Epub 2020 Jul 17.

Consultant Psychiatrist and Addictions Specialist, Addiction Services, Capital and Coast District Health Board, Wellington.

Orphanet J Rare Dis 2020 02 21;15(1):56. Epub 2020 Feb 21.

Norwegian Organisation for Quality Improvement of Laboratory Examinations (NOKLUS), Haraldsplass Deaconess Hospital, Bergen, Norway.

Background: Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population.

Methods: In a nationwide cohort study from 1992 to 2017, records of 333 persons (total person-years = 6728) with a confirmed AHP diagnosis were linked to several national compulsory registries (reference population = 5,819,937). Read More

Ann Hematol 2019 Dec 19;98(12):2683-2691. Epub 2019 Nov 19.

EPNET Clinical Center Munich, Hematology Oncology Center and Ludwig Maximilians University Munich, Zweibrückenstr.2, 80331, Munich, Germany.

In Germany, analyses of clinical and laboratory features of patients with acute porphyrias are only available for hereditary coproporphyria (HCP) but not with other acute porphyrias, acute intermittent porphyria (AIP) and variegate porphyria (VP). The aim of the study was to analyze a large cohort of patients with particular focus upon quality of life aspects. Sixty-two individuals from separate families with acute porphyrias (57 AIP, 5 VP) were included into an observational study collecting biochemical, genetic, and clinical data. Read More

Mol Genet Metab 2019 11 1;128(3):242-253. Epub 2019 Nov 1.

Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, United States of America.. Electronic address:

Background And Aim: An association between neuropsychiatric manifestations and neuroimaging suggestive of posterior reversible encephalopathy syndrome (PRES) during porphyric attacks has been described in numerous case reports. We aimed to systematically review clinical-radiological features and likely pathogenic mechanisms of PRES in patients with acute hepatic porphyrias (AHP) and porphyric attacks.

Methods: PubMed, Scopus, Ovid MEDLINE, and Google Scholar were searched (July 30, 2019). Read More

Int J Neurosci 2019 Dec 1;129(12):1226-1233. Epub 2019 Sep 1.

Department of Physiology and Biophysics, Stony Brook University Renaissance School of Medicine , New York , NY , USA.

Porphyrias are inherited disorders of the heme biosynthetic pathway, usually characterized by dermatological changes due to the accumulation of byproducts in the pathway. Select porphyrias also affect the nervous system, namely hereditary coproporphyria, acute intermittent porphyria and variegate porphyria. Complications include paralysis, hyponatremia which can risk central pontine myelinolysis, seizures and coma. Read More

Mol Genet Metab 2019 11 22;128(3):164-177. Epub 2019 Apr 22.

Division of Hematology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States of America. Electronic address:

Porphyrias, is a general term for a group of metabolic diseases that are genetic in nature. In each specific porphyria the activity of specific enzymes in the heme biosynthetic pathway is defective and leads to accumulation of pathway intermediates. Phenotypically, each disease leads to either neurologic and/or photocutaneous symptoms based on the metabolic intermediate that accumulates. Read More

J Eur Acad Dermatol Venereol 2020 Jan 16;34(1):184-187. Epub 2019 Jul 16.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: From a dermatologist's perspective, there are four major types of cutaneous porphyrias (CPs): porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Scarce data are available regarding the epidemiology of CPs.

Objectives: To describe the epidemiology of CPs in Israel, including distribution, incidence and prevalence rates of major types. Read More

Scand J Clin Lab Invest 2019 Sep 1;79(5):305-313. Epub 2019 Jun 1.

a Institute of Laboratory Medicine, Triemli Hospital , Zurich , Switzerland.

Molecular diagnosis of autosomal dominant acute hepatic porphyrias (AHPs) plays an important role in the management of these disorders. To introduce next generation sequencing (NGS) to the porphyria diagnosis, we designed a panel that contained four genes, , and for mutational analysis of acute intermittent porphyria (AIP), hereditary coproporphyria (HCP) and variegate porphyria (VP). To validate the AHP panel, 30 samples with known pathogenic variants as determined by Sanger sequencing, were analyzed using the Ion PGM™. Read More

Mol Genet Metab 2019 11 20;128(3):228-235. Epub 2019 May 20.

Section on Gastroenterology & Hepatology, Wake Forest University/NC Baptist Medical Center, Winston-Salem, NC, United States of America. Electronic address:

Background And Aims: The acute porphyrias are characterized by defects in heme synthesis, particularly in the liver. In some affected patients, there occurs a critical deficiency in a regulatory heme pool within hepatocytes that leads to up-regulation of 5-aminolevulinic acid [ALA] synthase-1, which is the first and normally rate-controlling enzyme in the pathway. In earlier work, we described defects in mitochondrial functions in cultured skin fibroblasts from patients with acute intermittent porphyria [AIP]. Read More

Gastroenterology 2019 08 11;157(2):365-381.e4. Epub 2019 May 11.

Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address:

Physicians should be aware of porphyrias, which could be responsible for unexplained gastrointestinal, neurologic, or skin disorders. Despite their relative rarity and complexity, most porphyrias can be easily defined and diagnosed. They are caused by well-characterized enzyme defects in the complex heme biosynthetic pathway and are divided into categories of acute vs non-acute or hepatic vs erythropoietic porphyrias. Read More

Genet Med 2019 11 10;21(11):2605-2613. Epub 2019 May 10.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information. Read More

Mol Genet Metab 2019 11 6;128(3):213-218. Epub 2019 Mar 6.

Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, NC 27157, United States of America.

The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes. Read More

Gastroenterol Hepatol 2019 Aug - Sep;42(7):438-439. Epub 2019 Apr 1.

Servicio de Medicina Interna, Hospital San Cecilio, Granada, España.

Hepatol Commun 2019 Feb 20;3(2):193-206. Epub 2018 Dec 20.

Section of Gastroenterology and Hepatology, Department of Internal Medicine Wake Forest University School of Medicine Winston-Salem NC.

The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Read More