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J Clin Neurol 2022 May;18(3):361-363

Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.

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

Clin Med (Lond) 2022 May;22(3):280-281

University Hospital of Badajoz, Badajoz, Spain.

A 40-year-old man attended the emergency room with abdominal pain and inappropriate behaviour associated with stress, and the consumption of alcohol and cannabis. Examination revealed hypertension (155/100 mmHg), tachycardia (95 beats per minute), abdominal pain and leucocytosis with neutrophilia, hyponatraemia and hypokalaemia. Urine was positive for nitrites, elevated bilirubin and cannabinoids. 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

Indian J Crit Care Med 2022 Mar;26(3):390-394

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

Acute intermittent porphyria (AIP) is autosomal dominant metabolic disorder of adulthood with limited case reports in children. Literature review from Western countries shows that most children present with non-specific gastrointestinal and neuropsychiatric symptoms with no family history. Moreover, the attacks are recurrent and precipitated by various factors (drugs/infection). Read More

QJM 2022 Apr 28. Epub 2022 Apr 28.

Address: 4th floor, F block, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Nehru Hospital, Sector, 12, Chandigarh (India) (160012).

QJM 2022 Apr 19. Epub 2022 Apr 19.

Digestive Department, the First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Taijiang District, Fuzhou, Fujian 350005, P.R. China.

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

Neurohospitalist 2022 Apr 9;12(2):377-382. Epub 2022 Feb 9.

University of Florida, Gainesville, FL, USA.

Porphyria is a metabolic disorder caused by a mutation in the heme biosynthetic pathway, with vague symptomatology and rare prevalence. A triad of hyponatremia, intermittent seizures, and abdominal pain should raise suspicion for porphyria. The diagnosis is based on increased blood porphobilinogen levels and genetic mutations. Read More

Orphanet J Rare Dis 2022 04 7;17(1):160. Epub 2022 Apr 7.

Department of Surgical and Medical Sciences for Children and Adults, Internal Medicine Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.

Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Read More

Anaesthesist 2022 Apr 29;71(4):321-330. Epub 2022 Mar 29.

Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Deutschland.

Porphyrias are a group of rare, mostly inherited metabolic disorders of heme biosynthesis. Each type of porphyria results from a specific deficiency of one of the pathway enzymes, causing a characteristic accumulation and excretion of heme precursors. Diagnosis is confirmed by the biochemical detection of these porphyrins and the precursors in urine, feces and blood. Read More

Int J Mol Sci 2022 Mar 16;23(6). Epub 2022 Mar 16.

Applied Metabolomics Research Group, IMIM, Hospital del Mar, Doctor Aiguader 88, 08003 Barcelona, Spain.

Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. Read More

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

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

Br J Pharmacol 2022 Feb 15. Epub 2022 Feb 15.

Pharmacometrics & Systems Pharmacology, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.

Background And Purpose: Acute intermittent porphyria (AIP) is a rare disease caused by a genetic mutation in the hepatic activity of the porphobilinogen-deaminase. We aimed to develop a mechanistic model of the enzymatic restoration effects of a novel therapy based on the administration of different formulations of recombinant human-PBGD (rhPBGD) linked to the ApoAI lipoprotein. This fusion protein circulates in blood, incorporating into HDL and penetrating hepatocytes. Read More

MMW Fortschr Med 2022 Feb;164(Suppl 4):6-8

MVZ Labor PD Dr. med. Volkmann GbR, Karlsruhe, Deutschland.

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

World J Transplant 2022 Jan;12(1):8-14

Nefrologia e Dialisi, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste 34100, Italy.

Background: Acute intermittent porphyria (AIP) is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population. AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase (PBGD) activity. Acute attacks are provoked by stressors such as certain medications, alcohol, and infection. Read More

J Intern Med 2022 May 23;291(5):593-610. Epub 2022 Jan 23.

Department of Medical Biochemistry and Biophysics, Centre for inherited Metabolic Diseases, Porphyria Centre Sweden., Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Acute hepatic porphyria (AHP) is a group of inherited metabolic disorders that affect hepatic heme biosynthesis. They are associated with attacks of neurovisceral manifestations that can be life threatening and constitute what is considered an acute porphyria attack. Until recently, the sole specific treatment for acute porphyria attacks consisted of the intravenous administration of hemin. Read More

Mol Genet Metab 2022 03 10;135(3):206-214. Epub 2022 Jan 10.

Université de Paris, INSERM U1149, Centre de Recherche sur l’Inflammation, F-75018 Paris, France

Background: In patients with acute intermittent porphyria (AIP), induction of delta aminolevulinic acid synthase 1 (ALAS1) leads to haem precursor accumulation that may cause recurring acute attacks. In a recent phase III trial, givosiran significantly reduced the attack rate in severe AIP patients. Frequent adverse events were injection-site reaction, fatigue, nausea, chronic kidney disease and increased alanine aminotransferase. Read More

Sci Transl Med 2022 01 12;14(627):eabc0700. Epub 2022 Jan 12.

Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.

Correction of enzymatic deficits in hepatocytes by systemic administration of a recombinant protein is a desired therapeutic goal for hepatic enzymopenic disorders such as acute intermittent porphyria (AIP), an inherited porphobilinogen deaminase (PBGD) deficiency. Apolipoprotein A-I (ApoAI) is internalized into hepatocytes during the centripetal transport of cholesterol. Here, we generated a recombinant protein formed by linking ApoAI to the amino terminus of human PBGD (rhApoAI-PBGD) in an attempt to transfer PBGD into liver cells. 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

N Engl J Med 2021 Dec;385(25):2378-2388

From the Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham (L.L.W.); and the Departments of Medicine (G.K.B., R.K.L., A.K.D.) and Radiology (R.C.), Massachusetts General Hospital, and the Departments of Medicine (G.K.B., R.K.L., R.H.G., A.K.D.) and Radiology (R.C.), Harvard Medical School, Boston, and the Department of Medicine, Cambridge Health Alliance, Cambridge (R.H.G.) - all in Massachusetts.

Mol Genet Metab Rep 2021 Dec 12;29:100818. Epub 2021 Nov 12.

Medical Research Council Toxicology Unit, University of Cambridge, United Kingdom.

Regulation of 5-aminolevulinate synthase 1 (ALAS1) for nonerythroid heme is critical for respiration, cell signaling mechanisms and steroid/drug metabolism. ALAS1 is induced in some genetic disorders but unlike other genes in the heme pathway, a gene variant of associated with inherited disease has not been reported. BALB/c mice carrying a null allele caused by a insert were developed and used to determine the consequences of heme demand of a semi gene copy number. Read More

Brain Nerve 2021 Dec;73(12):1333-1339

Department of Neurology, Gifu University Graduate School of Medicine.

There are many theories about Van Gogh's illness, including temporal lobe epilepsy, schizophrenia, Meniere's disease, manic depression, digitalis/absinthe poisoning, and acute intermittent porphyria, which, along with the truth of the ear-cutting incident, remain a great mystery. Van Gogh is often described as an "artist of madness and passion," but except for seven episodes of severe mental disturbance, his extraordinary creativity was maintained to the end. Reading "Van Gogh's Letters" reveals a very thoughtful and intelligent Van Gogh, far from being insane. Read More

Internist (Berl) 2022 Feb 11;63(2):224-229. Epub 2021 Nov 11.

Abteilung für Endokrinologie, Diabetologie, Porphyrie, Stadtspital Zürich Triemli, Birmensdorferstrasse 489, 8063, Zürich, Schweiz.

The acute porphyrias are a group of four metabolic defects in which the heme synthesis in the liver is disrupted. They are characterized by massively painful acute attacks, which can be life-threatening if not diagnosed. To raise the awareness for these rare disorders, a heme molecule in cartoon style is introduced, which accurately explains the basic biochemical processes in the body and mediates important information on the acute hepatic porphyrias in a simplified and attractive way. Read More

Acta Crystallogr F Struct Biol Commun 2021 Nov 19;77(Pt 11):388-398. Epub 2021 Oct 19.

Department of Chemistry, University of Manchester, Manchester M13 9PL, United Kingdom.

The enzyme hydroxymethylbilane synthase (HMBS; EC 4.3.1. 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

Liver Int 2022 01 16;42(1):161-172. Epub 2021 Nov 16.

Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Background & Aims: Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria.

Aims: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria.

Methods: Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Read More

Front Pharmacol 2021 6;12:712305. Epub 2021 Oct 6.

Department of Pharmacy, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.

This study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (HA) infusions in reducing attack frequency and severity in female AIP patients. We report the results of five female AIP patients with frequent recurrent attacks (>9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight). All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about AIP. Read More