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Biomedicines 2022 Mar 11;10(3). Epub 2022 Mar 11.

General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pad. Granelli, Via F Sforza 35, 20122 Milan, Italy.

Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by the hepatic deficiency of porphobilinogen deaminase (PBGD) and the slowdown of heme biosynthesis. AIP symptomatology includes life-threatening, acute neurovisceral or neuropsychiatric attacks manifesting in response to precipitating factors. The latter promote the upregulation of 5-aminolevulinic acid synthase-1 (ALAS1), the first enzyme of heme biosynthesis, which promotes the overload of neurotoxic porphyrin precursors. Read More

J Dtsch Dermatol Ges 2022 Mar;20(3):316-331

Department of Dermatology, Venereology and Allergology, University Hospital Göttingen, Göttingen, Germany.

The porphyrias are clinically variable and genetically heterogeneous, predominantly hereditary metabolic diseases, which are caused by a dysfunction of specific enzymes in heme biosynthesis. Here, we provide an overview of the etiopathogenesis, clinic, differential diagnosis, laboratory diagnostics and therapy of these complex metabolic disorders and cover in detail the most common form of porphyria worldwide (porphyria cutanea tarda), the most frequent childhood porphyria (erythropoietic protoporphyria), and the most common neurocutaneous porphyria (variegate porphyria). Read More

Diagnostics (Basel) 2022 Jan 8;12(1). Epub 2022 Jan 8.

Dipartimento di Medicina Interna, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inherited disorders resulting from defects in two different enzymes of the heme biosynthetic pathway, i.e., ferrochelatase (FECH) and delta-aminolevulinic acid synthase-2 (ALAS2), respectively. Read More

Int J Health Policy Manag 2021 Oct 13. Epub 2021 Oct 13.

Health Technology and Services Research Department, Technical Medical Centre, University of Twente, Enschede, The Netherlands.

Background: In some countries, such as the Netherlands and Norway, point-of-care testing (POCT) is more widely implemented in general practice compared to countries such as England and Australia. To comprehend what is necessary to realize the benefits of POCT, regarding its integration in primary care, it would be beneficial to have an overview of the structure of healthcare operations and the transactions between stakeholders (also referred to as value networks). The aim of this paper is to identify the current value networks in place applying to POCT implementation at general practices in England, Australia, Norway and the Netherlands and to compare these networks in terms of seven previously published factors that support the successful implementation, sustainability and scale-up of innovations. 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

Diagnostics (Basel) 2021 Jul 26;11(8). Epub 2021 Jul 26.

EPIGET-Epidemiology, Epigenetics, and Toxicology Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. 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

Drug Metab Dispos 2021 Jun 21. Epub 2021 Jun 21.

Alnylam Pharmaceuticals Inc., United States.

Conjugation of oligonucleotide therapeutics, including small interfering ribonucleic acids (siRNAs) or antisense oligonucleotides (ASOs) to N-acetylgalactosamine (GalNAc) ligands has become the primary strategy for hepatocyte-targeted delivery, and with the recent approvals of GIVLAARI® (givosiran) for the treatment of acute hepatic porphyria, OXLUMO (lumasiran) for the treatment of primary hyperoxaluria, and Leqvio® (inclisiran) for the treatment of hypercholesterolemia, the technology has been well-validated clinically. While much knowledge has been gained over decades of development there is a paucity of published literature on the DMPK properties of GalNAc-siRNA. With this in mind the goals of this mini-review are to provide an aggregate analysis of these nonclinical ADME data to build confidence on the translation of these properties to human. 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

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

Clin Rev Allergy Immunol 2019 Feb;56(1):32-40

Department of Dermatology, The University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-9069, USA.

Photo-contact dermatitis (PCD) describes the adverse cutaneous reaction that occurs in some patients as a result of simultaneous exposure to a contactant and to light. PCD can be subdivided into photo-allergic and photo-irritant dermatitis depending on whether the contactant respectively invokes an allergic or irritant reaction. Photo-irritant reactions are commonly caused by plants, psoralens, and medications taken internally, whereas photo-allergic reactions are commonly caused by sunscreens and topical nonsteroidal anti-inflammatory medications. Read More

F1000Res 2017 30;6:1906. Epub 2017 Oct 30.

Scottish Cutaneous Porphyria Service, Scottish Photodiagnostic Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin-haem biosynthetic pathway. Read More

Acta Derm Venereol 2016 Nov;96(7):868-872

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark.

Porphyrias are rare diseases caused by altered haem synthesis leading to the accumulation of different haem intermediates. Neurovisceral attacks may occur in acute porphyrias, while photosensitivity is the presenting symptom in cutaneous porphyrias. We present here an overview of symptoms and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. Read More

Hautarzt 2016 Mar;67(3):221-5

Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

Porphyrias comprise a heterogeneous group of predominantly genetically determined metabolic diseases which are due to a dysfunction in heme biosynthesis. Variegate porphyria and hereditary coproporphyria are referred to as neurocutaneous porphyrias because affected patients can develop both cutaneous symptoms on light-exposed body sites and potentially life-threatening acute neurovisceral symptoms, thereby mimicking several other diseases. In this overview, we provide an update on pathogenesis, clinical manifestation, diagnosis, and therapy of these two types of porphyria. Read More

Hautarzt 2016 Mar;67(3):201-6

Hautklinik und Europäisches Porphyriezentrum, Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Universitätsklinikum Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

The porphyrias comprise a clinically, biochemically, and genetically heterogeneous group of predominantly hereditary metabolic disorders resulting from a dysfunction along the heme biosynthetic pathway. Whereas most variants can manifest with different cutaneous symptoms, some types only reveal life-threatening acute neurovisceral attacks. Therefore, interdisciplinary care of these patients is advisable. Read More

Curr Protoc Hum Genet 2015 Jul 1;86:17.20.1-17.20.26. Epub 2015 Jul 1.

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas.

Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. Precisely which of these chemicals builds up depends on the type of porphyria. Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), δ-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). Read More

Eur J Hum Genet 2016 Jan 25;24(1):66-72. Epub 2015 Mar 25.

National Institute of Rheumatic Diseases, Piešťany, Slovakia.

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. Read More

Chembiochem 2014 Sep 4;15(14):2024-35. Epub 2014 Sep 4.

Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, Brühler Strasse 7, 53119 Bonn (Germany).

More than 20 years of research on heme as a temporary effector molecule of proteins have revealed its widespread impact on virtually all primary functions in the human organism. As our understanding of this influence is still growing, a comprehensive overview of compiled data will give fresh impetus for creativity and developing new strategies in heme-related research. From known data concerning heme-regulated proteins and their involvement in the development of diseases, we provide concise information of Fe(II/III) heme as a regulator and the availability of "regulatory heme". Read More

Tidsskr Nor Laegeforen 2014 Apr 29;134(8):831-6. Epub 2014 Apr 29.

Nasjonalt kompetansesenter for porfyrisykdommer (NAPOS) Laboratorium for klinisk biokjemi Haukeland universitetssykehus.

Background: Porphyria is an umbrella term for a group of largely hereditary diseases that are due to defective haem synthesis. The diseases have a varied and partly overlapping range of symptoms and presentations. The commonest forms of porphyria are porphyria cutanea tarda, acute intermittent porphyria and erythropoietic protoporphyria. Read More

Hepatology 2014 Sep 29;60(3):1082-9. Epub 2014 Jul 29.

Division of Gastroenterology and Hepatology, University of Alabama (UAB), Birmingham, AL.

Unlabelled: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Read More

Arch Dermatol Res 2014 May 24;306(4):313-330. Epub 2013 Oct 24.

Department of Dermatology, University of California at Davis, 3301 C Street, Sacramento, CA 95816, USA.

Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft-versus-host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. Read More

J Pediatr Hematol Oncol 2013 May;35(4):e167-70

Department of Pediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, India.

Congenital erythropoietic porphyria is a rare disorder of heme biosynthesis, resulting from decreased enzymatic activity of uroporphyrinogen III synthase. Clinical manifestations are heterogenous, of variable severity, and with occasional phenotypic-genotypic correlation. A 14-month-old boy developed fever, extensive dermatitis, and reddish colored urine. Read More

Clin Neurophysiol 2011 Dec 19;122(12):2336-44. Epub 2011 Aug 19.

School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.

The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Read More

Prim Care Companion CNS Disord 2011 ;13(6)

Department of Internal Medicine and Psychiatry (Drs Jain and Resch), Department of Psychiatry (Dr Bennett), and Department of Internal Medicine, Division of Hematology and Oncology, Simmons Cancer Institute (Dr Godwin), Southern Illinois University School of Medicine, Springfield.

Acute porphyrias are often misdiagnosed and most commonly present as atypical neuropsychiatric symptoms or acute abdominal pain. Clinicians should suspect acute porphyrias in patients presenting with variable neuropsychiatric symptoms and unexplained pain. Proper identification can lead to less iatrogenicity associated with porphyrinogenic agents, appropriate management, and a better patient outcome. Read More

Best Pract Res Clin Gastroenterol 2010 Oct;24(5):593-605

Department of Dermatology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

The porphyrias are predominantly inherited metabolic disorders, which result from a specific deficiency of one of the eight enzymes along the pathway of haem biosynthesis. Historically, they have been classified into hepatic and erythropoietic forms, based on the primary site of expression of the prevailing dysfunctional enzyme. From a clinical point of view, however, it is more convenient to subdivide them into acute and non-acute porphyrias, thereby primarily considering the potential occurrence of life-threatening acute neurovisceral attacks. Read More

Antonie Van Leeuwenhoek 2011 Mar 22;99(3):443-56. Epub 2010 Aug 22.

PROIMI - CONICET, Planta Piloto de Procesos Industriales Microbiológicos, Av Belgrano y Caseros, T4001MVB Tucumán, Argentina.

Microcosm assays with dye-amended culture media under a shot-feeding strategy allowed us to obtain 100 yeast isolates from the wastewater outfall channel of a dyeing textile factory in Tucumán (Argentina). Meanwhile, 63 yeast isolates were obtained from Phoebe porphyria (Laurel del monte) samples collected from Las Yungas rainforest (Tucumán), via a classical isolation scheme. Isolated yeasts, both from dye-polluted and virgin environments, were compared for their textile dye decolourization ability when cultured on solid and liquid media. Read More

Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):147-51. Epub 2009 Jul 1.

Porphyria Center Saxony, Medizinische Klinik II, Klinikum Chemnitz.

Acute porphyrias are caused by enzyme defects along the heme synthesis pathway. Patients usually present with abdominal pain, impaired intestinal motility, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine. This article gives an overview over drugs that are recommended in patients with acute hepatic porphyrias and represents a compilation of four so far existing lists. Read More

Cell Mol Biol (Noisy-le-grand) 2009 Jul 1;55(2):79-88. Epub 2009 Jul 1.

Dipartimento di Medicina Interna, Università degli Studi di Milano - Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena IRCCS Milano, Italy.

Variegate Porphyria (VP) is an autosomal dominant disorder found worldwide but is rare in Italy. In this study we provide an overview of clinical, biochemical and genetic background of 33 Italian VP patients diagnosed in the last fifteen years. About 70% of patients had experienced clinical symptoms: 43. Read More

Curr Opin Neurol 2008 Oct;21(5):563-8

Department of Neurology, University of Würzburg, Germany.

Purpose Of Review: To give an overview of recent data on the use of skin biopsy as a diagnostic tool in neuropathies.

Recent Findings: The sensitivity and specificity of skin biopsy in detecting small fiber neuropathy is supported by new data. In many patients with small fiber neuropathy, a treatable disorder can be identified if a full workup is done. Read More

J Inherit Metab Dis 2007 Oct 10;30(5):631-41. Epub 2007 Aug 10.

Federation of Nervous System Diseases, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75651, Paris cedex 13, France.

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood as a psychiatric disorder. In some instances, an IEM is suspected because of informative family history or because psychiatric symptoms form part of a more diffuse clinical picture with systemic, cognitive or motor neurological signs. However, in some cases, psychiatric signs may be apparently isolated. Read More