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Mediterr J Hematol Infect Dis 2019 1;11(1):e2019018. Epub 2019 Mar 1.

National Institute of Immunohaematology, 13 the floor KEM hospital MS building, Parel, Mumbai 400012, Maharashtra, India.

An otherwise healthy male child of 9 years presented with paroxysmal fever and diffuse abdominal pain along with the loss of appetite and nausea lasting for 3-4 days every 4-6 weeks in the last two years. He also has stretchable skin and hypermobile joints, inherited from his mother who never suffered any paroxysmal attack of the kind. Work up for acute intermittent porphyria, lead poisoning, and familial Mediterranean fever was negative. Read More

Neurol Sci 2019 Mar 1. Epub 2019 Mar 1.

Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Recent advances in pathophysiological and genetic mechanisms of some neuromuscular diseases and a rapid progress in new pharmacological technologies led to an accelerated development of innovative treatments, generating an unexpected therapeutic revolution. In part 1, we report already commercially available drugs, just approved drugs and new therapeutic promises in the treatment of peripheral neuropathies. Hereditary transthyretin amyloidosis (hATTR) is a devastating disease due to amyloid accumulation in peripheral nerves, heart and autonomic system. Read More

Orphanet J Rare Dis 2019 Feb 26;14(1):59. Epub 2019 Feb 26.

CIBERER-ISCIII, Madrid, Spain.

Background: Acute intermittent porphyria (AIP) is a low-penetrant genetic metabolic disease caused by a deficiency of hydroxymethylbilane synthase (HMBS) in the haem biosynthesis. Manifest AIP (MAIP) is considered when carriers develop typical acute neurovisceral attacks with elevation of porphyrin precursors, while the absence of attacks is referred to as latent AIP (LAIP). Attacks are often triggered by drugs, endocrine factors, fasting or stress. Read More

Gut 2019 Feb 22. Epub 2019 Feb 22.

Instituto de Investigación Sanitaria de Navarra IdiSNA, Pamplona, Spain.

Decades of intense research in molecular biology and biochemistry are fructifying in the emergence of therapeutic messenger RNAs (mRNA) as a new class of drugs. Synthetic mRNAs can be sequence optimised to improve translatability into proteins, as well as chemically modified to reduce immunogenicity and increase chemical stability using naturally occurring uridine modifications. These structural improvements, together with the development of safe and efficient vehicles that preserve mRNA integrity in circulation and allow targeted intracellular delivery, have paved the way for mRNA-based therapeutics. Read More

Zh Nevrol Psikhiatr Im S S Korsakova 2019 ;119(1):72-75

Perm Regional clinical Hospital, Perm, Russia.

The authors describe a rare and diagnostically difficult variant of neurological symptoms of acute intermittent porphyria complicated by rhabdomyolysis. Diagnostic criteria of the disease are highlighted. A differential diagnosis with diseases with similar clinical manifestation was made. Read More

Mol Genet Metab 2019 Jan 6. Epub 2019 Jan 6.

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

Acute Intermittent Porphyria (AIP), an autosomal dominant hepatic disorder, results from hydroxymethylbilane synthase (HMBS) mutations that decrease the encoded enzymatic activity, thereby predisposing patients to life-threatening acute neurovisceral attacks. The ~1% penetrance of AIP suggests that other genetic factors modulate the onset and severity of the acute attacks. Here, we characterized the hepatic transcriptomic response to phenobarbital (PB) administration in AIP mice, which mimics the biochemical attacks of AIP. Read More

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

J Inherit Metab Dis 2019 Jan;42(1):186-194

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue Room 14-34, New York, NY 10029, USA.

Acute intermittent porphyria (AIP), an autosomal dominant disorder due to the half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by acute neurovisceral attacks that are precipitated by factors that induce heme biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic test for AIP, and importantly, it permits the identification of asymptomatic family members for genetic counseling and avoidance of precipitating factors. Here, we report the identification of 40 novel HMBS mutations, including 11 missense, four nonsense, 16 small insertions or deletions, eight consensus splice site mutations, and a complex insertion-deletion mutation in unrelated individuals with AIP. Read More

Mol Genet Metab 2019 Jan 18. Epub 2019 Jan 18.

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

Mouse models of the human porphyrias have proven useful for investigations of disease pathogenesis and to facilitate the development of new therapeutic approaches. To date, mouse models have been generated for all major porphyrias, with the exception of X-linked protoporphyria (XLP) and the ultra rare 5-aminolevulinic acid dehydratase deficient porphyria (ADP). Mouse models have been generated for the three autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Read More

Mol Genet Metab Rep 2019 Jun 30;19:100450. Epub 2019 Jan 30.

Department of Medicine, Wake Forest University/NC Baptist Medical Center, Winston-Salem, NC, United States.

Acute intermittent porphyria (AIP), an autosomal dominant inborn error of metabolism, is the most common and severe form of the acute porphyrias. Attacks of severe abdominal pain, often with hypertension, tachycardia, are cardinal features of AIP, often requiring hospital admissions. Frequent recurrent attacks of AIP, defined as >3 attacks in one year, during which at least one attack requires intravenous heme therapy, are associated with significant morbidity, lost productivity, and health care burden. Read More

N Engl J Med 2019 02;380(6):549-558

From the Porphyria Centre Sweden, Karolinska Institutet, Karolinska University Hospital, Stockholm (E.S., P.H., D.V.); Icahn School of Medicine at Mount Sinai, New York (M.B., R.D.); King's College Hospital, London (P.S., D.R.); University of California, San Francisco, San Francisco (D.M.B.); University of Utah, Salt Lake City (C. Parker, J.P.); Wake Forest University, Winston-Salem, NC (H.L.B.); Alnylam Pharmaceuticals, Cambridge, MA (C. Penz, A.C.-D., Q.H., W.Q., K.F., J.B.K., P.G., A.V., A.R.S.); and the University of Texas Medical Branch at Galveston, Galveston (K.E.A.).

Background: Induction of delta aminolevulinic acid synthase 1 ( ALAS1) gene expression and accumulation of neurotoxic intermediates result in neurovisceral attacks and disease manifestations in patients with acute intermittent porphyria, a rare inherited disease of heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.

Methods: We conducted a phase 1 trial of givosiran in patients with acute intermittent porphyria. Read More

Ann Intern Med 2019 Feb 5. Epub 2019 Feb 5.

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (H.A., D.J.K.).

Scand J Urol 2019 Feb 4:1-3. Epub 2019 Feb 4.

a Faculty of Health Sciences , UiT The Arctic University of Norway , Troms⊘ , Norway.

Ann Dermatol Venereol 2019 Feb 30;146(2):143-159. Epub 2019 Jan 30.

Service de dermatologie, CHR Metz-Thionville, 1, allée du Château, CS 45001, 57085 Metz cedex 03, France. Electronic address:

The porphyrias are a group of metabolic disorders resulting from an innate abnormality in haem biosynthesis, and the clinical settings of which vary according to the genetic enzyme abnormality in question. These are genetic disorders with autosomal dominant or recessive inheritance of varying penetrance, and whose clinical expression differs according to the preferential location of haem precursors. Different classifications have been proposed according to genetic inheritance, the enzyme anomaly at issue, and clinical expression. Read More

Epilepsy Behav Case Rep 2019 28;11:43-46. Epub 2018 Nov 28.

Department of Neurology, Mayo Clinic, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA.

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic-clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. Read More

Transplant Proc 2019 Jan - Feb;51(1):229-234. Epub 2018 Jun 30.

Surgical, Medical and Dental Department of Morphological Sciences, Section of Nephrology, University of Modena and Reggio Emilia, Modena, Italy.

Rhodococcus equi is a gram-positive coccobacillus responsible for severe infections in patients with weakened immune systems. R equi generally causes pnumonia that may evolve into fatal systemic infection if left untreated. Here, we present a case of a 67-year-old woman affected by acute intermittent porphyria (AIP) who developed R equi pneumonia 7 months after kidney transplantation. Read More

Mol Genet Metab 2019 Jan 7. Epub 2019 Jan 7.

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

Background And Aims: Acute intermittent porphyria (AIP) results from a partial deficiency of porphobilinogen deaminase (PBGD). Symptomatic AIP patients, most of whom are women, experience acute attacks characterized by severe abdominal pain and abrupt increases in blood pressure. Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice. Read More

Mol Genet Metab 2018 Dec 21. Epub 2018 Dec 21.

Pharmacometrics & Systems Pharmacology Research Unit, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.

Introduction: Acute intermittent porphyria (AIP) is characterized by hepatic over-production of the heme precursors when aminolevulinic acid (ALA)-synthase 1 is induced by endogenous or environmental factors. The aim of this study was to develop a semi-mechanistic computational model to characterize urine accumulation of heme precursors during acute attacks based on experimental pharmacodynamics data and support the development of new therapeutic strategies.

Methods: Male AIP mice received recurrent phenobarbital challenge starting on days 1, 9, 16 and 30. Read More

Hum Mol Genet 2019 Jan 7. Epub 2019 Jan 7.

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

Acute intermittent porphyria (AIP) is an inborn error of heme biosynthesis due to the deficiency of hydroxymethylbilane synthase (HMBS) activity. Human AIP heterozygotes have episodic acute neurovisceral attacks that typically start after puberty, whereas patients with homozygous dominant AIP (HD-AIP) have early-onset chronic neurological impairment, including ataxia and psychomotor retardation. To investigate the dramatically different manifestations, knock-in mice with human HD-AIP missense mutations c. Read More

Mol Genet Metab 2018 Nov 30. Epub 2018 Nov 30.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address:

The inborn errors of heme biosynthesis, the Porphyrias, include eight major disorders resulting from loss-of-function (LOF) or gain-of-function (GOF) mutations in eight of the nine heme biosynthetic genes. The major sites of heme biosynthesis are the liver and erythron, and the underlying pathophysiology of each of these disorders depends on the unique biochemistry, cell biology, and genetic mechanisms in these tissues. The porphyrias are classified into three major categories: 1) the acute hepatic porphyrias (AHPs), including Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and 5-Aminolevlulinic Acid Dehydratase Deficient Porphyria (ADP); 2) a hepatic cutaneous porphyria, Porphyria Cutanea Tarda (PCT); and 3) the cutaneous erythropoietic porphyrias, Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-Linked Protoporphyria (XLP). Read More

Mol Genet Metab 2018 Dec 10. Epub 2018 Dec 10.

Department of Laboratory Medicine, Nordland Hospital Trust, Bodø, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Lifestyle factors, including a low intake of carbohydrates, dieting, alcohol consumption, cigarette smoking and stress are some of the possible triggers of attacks in acute intermittent porphyria (AIP). The influence of lifestyle factors, including energy intake, diet and alcohol consumption on the biochemical disease activity in AIP and biochemical nutritional markers were examined.

Methods: A case-control study with 50 AIP cases and 50 controls matched for age, sex and place of residence was performed. Read More

Am J Med Genet B Neuropsychiatr Genet 2019 Jan 16;180(1):46-54. Epub 2018 Dec 16.

Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Many genetic conditions can mimic mental health disorders, with psychiatric symptoms that are difficult to treat with standard psychotropic medications. This study tests the hypothesis that psychiatric populations are enriched for pathogenic variants associated with selected inborn errors of metabolism (IEMs). Using next-generation sequencing, 2046 psychiatric patients were screened for pathogenic variants in genes associated with four IEMs, Niemann-Pick disease type C (NPC), Wilson disease (WD), homocystinuria (HOM), and acute intermittent porphyria (AIP). Read More

Trends Mol Med 2019 Jan 6;25(1):3-5. Epub 2018 Dec 6.

UMRs 1149, Centre de Recherche sur l'Inflammation, Institut National de la Santé et de la Recherche Médicale, Université Paris Diderot, F-75018 Paris, France; Assistance Publique-Hôpitaux de Paris, HUPNVS Centre Français des Porphyries, Hôpital Louis Mourier, 178 Rue des Renouillers, F-92701 Colombes, France; Laboratory of Excellence Gr-Ex, 75015 Paris, France. Electronic address:

The potential of mRNA to produce therapeutic and protective protein levels is a promising approach for the treatment of a large number of diseases. In a recent study published in Nature Medicine (Published online October 8, 2018. doi. Read More

Psychiatr Danub 2018 Nov;30(Suppl 7):559-562

Clare College Cambridge, University of Cambridge, Trinity Lane, Cambridge, CB2 1TL, UK,

The geniuses Robert Schumann and Vincent Van Gogh show striking similarities both in the longitudinal nature of the progression of their illnesses, and the symptoms they experienced. There have been physiological explanations posed for both men, including Meniere's disease, tertiary syphilis, acute intermittent porphyria, terpenoid and lead poisoning, intracranial masses, temporal lobe epilepsy and dementia caused by vascular hypertension. The evidence for these physiological explanations is assessed. Read More

Mol Genet Metab 2018 Oct 9. Epub 2018 Oct 9.

UMRs 1149, Centre de Recherche sur l'Inflammation, Institut National de la Santé et de la Recherche Médicale, F-75018 Paris, France; Assistance Publique-Hôpitaux de Paris, HUPNVS Centre Français des Porphyries, Hôpital Louis Mourier, 178 Rue des Renouillers, F-92701 Colombes, France; Laboratory of Excellence Gr-Ex, France; Université Paris Diderot, UFR de Médecine Xavier Bichat, F-75018 Paris, France.

Porphyrias are inherited diseases with low penetrance affecting the heme biosynthesis pathway. Acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP) together constitute the acute hepatic porphyrias (AHP). These diseases have been identified as risk factors for primary liver cancers (PLC), mainly hepatocellular carcinoma (HCC: range 87-100%) but also cholangiocarcinoma, alone or combination with HCC. Read More

Mol Genet Metab 2018 Oct 26. Epub 2018 Oct 26.

Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, NY 10029, USA. Electronic address:

The acute hepatic porphyrias (AHPs) are inborn errors of heme biosynthesis, which include three autosomal dominant porphyrias, Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), and Variegate Porphyria (VP), and the ultra-rare autosomal recessive porphyria, δ-Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP). AIP, HCP, VP, and ADP each results from loss-of-function (LOF) mutations in their disease-causing genes: hydroxymethylbilane synthase (HMBS); coproporphyrinogen oxidase (CPOX); protoporphyrinogen oxidase (PPOX), and δ-aminolevulinic acid dehydratase (ALAD), respectively. During the 11-year period from January 1, 2007 through December 31, 2017, the Mount Sinai Porphyrias Diagnostic Laboratory diagnosed 315 unrelated AIP individuals with HMBS mutations, including 46 previously unreported mutations, 29 unrelated HCP individuals with CPOX mutations, including 11 previously unreported mutations, and 54 unrelated VP individuals with PPOX mutations, including 20 previously unreported mutations. Read More

Internist (Berl) 2018 Dec;59(12):1239-1248

MVZ Labor PD Dr. Volkmann und Kollegen GbR, 76133, Karlsruhe, Deutschland.

Porphyrias are caused by enzyme defects of heme biosynthesis. According to their clinical presentation and to each affected pathway, they are categorized into acute and non-acute as well as hepatic and erythropoietic porphyrias. Acute hepatic porphyrias, e. Read More

Nat Med 2018 Dec 8;24(12):1899-1909. Epub 2018 Oct 8.

Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.

Acute intermittent porphyria (AIP) results from haploinsufficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis pathway. Patients with AIP have neurovisceral attacks associated with increased hepatic heme demand. Phenobarbital-challenged mice with AIP recapitulate the biochemical and clinical characteristics of patients with AIP, including hepatic overproduction of the potentially neurotoxic porphyrin precursors. Read More

Cureus 2018 Jul 17;10(7):e2989. Epub 2018 Jul 17.

Internal Medicine, Shifa College Of Medicine, Islamabad, PAK.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system (CNS) with no distinct etiology but implications include infections and commonly administered vaccinations. In this case report, we present the case of ADEM in a young female who was subsequently diagnosed with acute intermittent porphyria (AIP) that was the instigator of the initial CNS assault. Our case highlights the peculiar presentation of ADEM which can present as a diagnostic challenge and brings forth AIP as a new and previously unknown affiliate of this rare CNS disease. Read More

Mol Biol Rep 2018 Dec 14;45(6):2801-2809. Epub 2018 Sep 14.

Laboratory of Molecular Biology, Butantan Institute, Av. Vital Brasil, 1500, Butantã, São Paulo, SP, 05503-900, Brazil.

Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver. Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a higher incidence of hepatocellular carcinoma (HCC) in AIP patients. Read More

Medicine (Baltimore) 2018 Sep;97(37):e12295

Shanxi Medical University.

Rationale: Acute intermittent porphyria (AIP) is caused by hydroxymethylbilane synthase (HMBS) gene mutation.

Patient Concerns: A Chinese female patient with very typical AIP symptoms of severe abdominal pain, seizures, hypertension, and tachycardia, accompanied with hyponatremia, anemia, and hyperbilirubinemia.

Diagnoses: She was diagnosed as AIP based on positive result of urine porphobilinogen and her clinical syndrome. Read More

Mol Genet Metab 2018 Nov 5;125(3):295-301. Epub 2018 Sep 5.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O.C. Medicina Generale, Milano, Italy. Electronic address:

Genetic variants in promoters and alternative-splicing lesions require to be experimentally tested in order to validate them as causatives of a disease. The digital PCR (dPCR) approach, which is an alternative to the classical qPCR, is an innovative and a more sensitive method for the detection and quantification of nucleic acids. In the present study, we identified four HMBS gene mutations affecting the ubiquitous isoform of porphobilinogen deaminase (PBGD) and established a dPCR protocol which would be able to detect the different transcripts of this gene. Read More

Medicine (Baltimore) 2018 Sep;97(36):e11665

Urology Department, Qilu Hospital of Shandong University, Qingdao, Shandong Province, China.

Introduction: Acute intermittent porphyria (AIP) is a rare and challenging hereditary neurovisceral disease with no specific symptoms. Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome with bilateral reversible posterior gyriform lesions that can be associated with many different conditions, including AIP. Usually, peripheral neuropathy is considered the most common neurological manifestation of AIP. Read More

Indian J Endocrinol Metab 2018 Jul-Aug;22(4):573-574

Department of Medicine, Dr. S. N. Medical College, Jodhpur, Rajasthan, India.

Hum Mol Genet 2018 11;27(21):3688-3696

Hepatology Program, CIMA-University of Navarra, Spain.

A first-in-human gene therapy trial using a recombinant adeno-associated viral (rAAV) vector for acute intermittent porphyria (AIP) reveals that higher doses would be required to reach therapeutic levels of the porphobilinogen deaminase (PBGD) transgene. We developed a hyperfunctional PBGD protein to improve the therapeutic index without increasing vector dose. A consensus protein sequence from 12 mammal species was compared to the human PBGD sequence, and eight amino acids were selected. Read More

BMC Res Notes 2018 Aug 2;11(1):552. Epub 2018 Aug 2.

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

Background: Acute intermittent porphyria is a rare autosomal dominant disorder caused by a deficiency of the enzyme, hydroxymethylbilane synthase. Recognition of acute neurovisceral attacks can be difficult due to the nonspecific nature of symptoms.

Case Presentation: We report a case of 33-year-old male patient who presented with recurrent episodes of severe abdominal pain, nausea, vomiting, constipation and numbness of bilateral lower limb extremities. Read More

J Inherit Metab Dis 2018 Nov;41(6):1297-1298

Porphyria Center, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.

Due to a typesetting error the wrong figure 2 was used. Read More

Patient 2018 10;11(5):527-537

Modus Outcomes, Newton, MA, USA.

Objective: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. Read More

J Family Med Prim Care 2018 Jan-Feb;7(1):261-263

Department of Pediatrics, Sri Aurobindo Medical College and Postgraduate Institute, Indore, Madhya Pradesh, India.

Acute intermittent porphyria (AIP) and ichthyosis vulgaris both are autosomal dominant disorders with incomplete penetrance caused by the deficiency of porphobilinogen deaminase enzyme and filaggrin protein, respectively. We report a rare case of a 9-year-old boy having two genetic diseases with an unclear association. An acute attack of AIP is characterized by gastrointestinal symptoms and neuropsychiatric manifestations. Read More

Biochim Biophys Acta Gen Subj 2018 09 15;1862(9):1948-1955. Epub 2018 Jun 15.

Protein Stability and Inherited Disease Laboratory, CIC bioGUNE, Derio, Bizkaia 48160, Spain. Electronic address:

Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo- and holo-enzyme bound to the cofactor. Read More

Biomed Res Int 2018 15;2018:3216802. Epub 2018 May 15.

Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.

Background: Acute intermittent porphyria (AIP) is an autosomal recessive disorder with intermittent attacks. Patients with AIP are susceptible to impaired quality of life and psychological distress.

Objectives: To document the clinical features of AIP and its impact on SF-36 and IES scores of AIP patients in China and to explore the variables associated with SF-36 and IES scores. Read More

Front Genet 2018 20;9:129. Epub 2018 Apr 20.

Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Hangzhou, China.

Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of gene causes AIP. Mutation of gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. Read More

J Inherit Metab Dis 2018 Sep 19;41(5):809-817. Epub 2018 Apr 19.

Porphyria Center, Center for Lysosomal and Metabolic Disease, Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.

Introduction: A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers.

Methods: Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. Read More

Clin Kidney J 2018 Apr 10;11(2):191-197. Epub 2018 Jan 10.

Centre Francais des Porphyries, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes, France.

The kidneys, after the bone marrow and liver, are third in terms of the amounts of haem synthesized daily. Haem is incorporated into haemoproteins that are critical to renal physiology. In turn, disturbances in haem metabolism interfere with renal physiology and are tightly interrelated with kidney diseases. Read More

Pediatrics 2018 05 10;141(5). Epub 2018 Apr 10.

Division of Hospital Medicine and.

An 18-year-old woman with a complex past medical history presented with 2 days of vomiting and lower abdominal pain. She had been admitted for the majority of the previous 5 months for recurrent pancreatitis and had undergone a cholecystectomy. Additional symptoms included nausea, anorexia, constipation, and a 40-lb weight loss over 4 months. Read More

Proc Natl Acad Sci U S A 2018 04 9;115(17):E4071-E4080. Epub 2018 Apr 9.

Life Sciences Division, TCS Innovation Labs-Hyderabad, Tata Consultancy Services Limited, Hyderabad 500081, India;

Hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway, catalyzes the head-to-tail condensation of four molecules of porphobilinogen (PBG) to form the linear tetrapyrrole 1-hydroxymethylbilane (HMB). Mutations in human () cause acute intermittent porphyria (AIP), an autosomal-dominant disorder characterized by life-threatening neurovisceral attacks. Although the 3D structure of hHMBS has been reported, the mechanism of the stepwise polymerization of four PBG molecules to form HMB remains unknown. Read More

J Inherit Metab Dis 2018 Mar 28. Epub 2018 Mar 28.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue Room 14-34, New York, NY, 10029, USA.

Acute intermittent porphyria (AIP), an autosomal dominant disorder due to the half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by acute neurovisceral attacks that are precipitated by factors that induce heme biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic test for AIP, and importantly, it permits the identification of asymptomatic family members for genetic counseling and avoidance of precipitating factors. Here, we report the identification of 40 novel HMBS mutations, including 11 missense, four nonsense, 16 small insertions or deletions, eight consensus splice site mutations, and a complex insertion-deletion mutation in unrelated individuals with AIP. Read More

Rambam Maimonides Med J 2018 04 19;9(2). Epub 2018 Apr 19.

Porphyria Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.

The porphyrias are a group of rare metabolic disorders, inherited or acquired, along the heme biosynthetic pathway, which could manifest with neurovisceral and/or cutaneous symptoms, depending on the defective enzyme. Neurovisceral porphyrias are characterized by acute attacks, in which excessive heme production is induced following exposure to a trigger. An acute attack usually presents with severe abdominal pain, vomiting, and tachycardia. Read More

Pract Neurol 2018 Oct 14;18(5):352-358. Epub 2018 Mar 14.

Department of Neurology, Sheffield Teaching Hospitals (STH), Sheffield, UK.

The diagnosis of acute intermittent porphyria (AIP) is often overlooked. We describe a patient with this condition who had all the 'bells and whistles', in whom the diagnosis was only made after considerable delay. Far from an esoteric condition haunting examination candidates, AIP is an important cause of a broad spectrum of neurological symptoms. Read More