Diagnosis Of Porphyria Research Articles

Diagnosis of Porphyria after Sternotomy for Severe Calcific Coronary Artery Disease : A Case Report

Diagnosis of Porphyria after Sternotomy for Severe Calcific Coronary Artery Disease : A Case Report

Ultraviolet Absorption Spectral Scan and Fluorescence Emission Spectral Scan Analysis: Potential Tests with Diagnostic Utility in Porphyria

ABSTRACT Introduction Symptoms of porphyria usually overlap with other clinical conditions, thereby leading to misdiagnosis and inappropriate treatment, especially when patient presents with uncommon features. An accurate diagnosis of porphyria can be made only when enzyme defects can be detected, which is costly and not easily available. Classically, Ehrlich's test used to screen porphyria has certain disadvantages too. Hence, we planned this study. Aim To develop comparatively simpler diagnostic tests feasible at tertiary care centers to work up porphyria cases. Materials and methods A suspected case of porphyria was screened using Ehrlich's test. Thereafter, patient's urine and serum samples were analyzed by ultraviolet (UV) absorption spectral scan and fluorescence emission spectral scan using multimode microplate reader and compared against normal controls to validate the results. Results The UV absorption spectral scan revealed a small peak at 410 nm for patient's urine sample, which intensified on acidification. The UV absorption spectral scan for patient's serum also showed absorbance peak at 405 nm vs normal serum. The fluorescence emission spectral scan of urine and serum of patient revealed a sharp emission peak at 626 nm, which was not present in respective samples of control. Fluorescence emission in patient's urine sample was 10.5 times more vs normal urine. Conclusion and clinical significance Novel methods like UV absorption spectral scan and fluorescence emission spectral scan using patient's urine and serum samples can be developed as diagnostic tests considering their practicality and affordability. Further, an algorithm formulated based on clinical features and basic lab tests can also identify the type of porphyria. How to cite this article Nimesh A, Agarwal V, Garg S, Mehndiratta M. Ultraviolet Absorption Spectral Scan and Fluorescence Emission Spectral Scan Analysis: Potential Tests with Diagnostic Utility in Porphyria. Indian J Med Biochem 2017;21(2):136-141.

Porphyria: Analysis of Register from Brazilian Association of Porphyria (ABRAPO)

1.1.Background:The porphyria is a group of rare metabolic disorders that arise from deficiencies in the heme biosynthetic pathway. The prevalence in Europe is 1-2:100,000 inhabitants. These disorders occur mostly due to mutations in the genes encoding enzymes involved in heme production. They are classified and divided into acute (ALA Dehydratase Deficiency [ALADP], Acute Intermittent Porphyria [AIP], Variegate Porphyria [VP], Hereditary Coproporphyria [HCP]), chronic (Congenital Erythropoietic Porphyria [CEP], Erythropoietic Porphyria [EPP], Porphyria Cutanea Tarda [PCT] and Hepato Erythropoietic Porphyria [HEP]). AIP is the most common form of hepatic porphyria and symptoms are often begin after puberty and consist of acute neurovisceral signs, abdominal pain, vomiting, constipation, tachycardia, fever, hypertension and alterations in the central nervous system. 1.2.Aim:To study the porphyria frequency in Brazil by Associacao Brasileira de Porfiria (ABRAPO- Brazilian Porphyria Association). 1.3.Methods:We study the frequency of porphyria in 439 cases of patients with porphyria diagnosis from ABRAPO from 2007 to 2015 and data were analyzed with Microsoft Excel® program. 1.4.Results:We analyzed 439 cases consisting of 74.2% female. 59% percent had been diagnosed with AIP, 22% PCT, 4% HCP, 4% EPP, 2.5% VP, 1.1% CEP, 0.9% HEP and 0.4% ALADP. 1.5.Conclusion:Our analysis revealed similar epidemiological characteristics as seen in the United States and United Kingdom. In Brazil, porphyria should be studied more carefully to assess, properly diagnosis and treatment.

Intermittently We Get Things Right: A Case of Porphyria After Esophagogastrectomy

Acute porphyrias are rare inherited metabolic disorders of heme production, intermittently presenting with abdominal pain and neurovisceral symptoms. We discuss the case of a 58-year-old African American female with a history of gastroparesis and esophageal adenocarcinoma, who presented with intractable abdominal pain, nausea and vomiting. Her symptoms were initially attributed to her previously established gastrointestinal diagnoses; however, an in-depth workup for gastric, hepatic, biliary and vascular causes was negative. Ultimately, a urine porphyria panel revealed elevated porphyrins and the patient was treated with a high carbohydrate diet and hemin infusion, with subsequent normalization of her urine porphyrins and improvement of her symptoms. Acute Porphyrias are exceedingly rare. However, the occurrence of acute porphyria after gastric surgery has been previously reported and attributed to diminished carbohydrate intake. Similarly, this patient's esophagogastrectomy reduced her caloric carbohydrate intake, perhaps resulting in the accumulation of heme precursors and the onset of a clinical crisis. The patient's dramatic normalization of urine porphyrins following hemin treatment underscores the validity of her diagnosis. Thus, we propose that acute porphyria should be considered in patients with recurrent abdominal pain, nausea and vomiting and a negative work-up for another intra-abdominal pathology. Porphyrias should also be considered in patients with persistent pain after abdominal surgery and those with reduced caloric intake. Early diagnosis of porphyria is key to effective treatment with hemin. Simple spot urine tests for urine porphinobilinogen, although not performed in this case due to low suspicion, can easily rule out the diagnosis, and should be the first step in the workup of such patients.Table 1: Urine porphyria panel results prior to hemin treatment and after hemin treatment. All values were initially elevated and were within normal levels after treatment. Urine ALA remained elevated 10 days after admission.

Acute porphyrias and porphyric neuropathy

The porphyrias are a group of uncommon inherited metabolic disorders of heme biosynthesis. Acute porphyrias are specific types of porphyrias characterized by the presence of acute attacks that usually present with abdominal pain, psychiatric symptoms, and neuropathy. The nonspecific porphyria presentations, the complexity of heme biosynthesis, and difficulty in interpreting the laboratory tests make the diagnosis of porphyria challenging. Treatment of acute porphyria and avoidance of precipitating factors should be initiated early to prevent potentially severe long-term sequelae from nerve damage. Porphyric neuropathy is one such complication and is characterized by an axonal neuropathy with predominant motor involvement. Sensory neuropathy is also found but is less common. Although the exact pathophysiology of porphyric neuropathy remains uncertain, neural energy failure from heme deficiency and neurotoxicity from porphyrin precursors are probably the two main mechanisms. The understanding of porphyric neuropathy and manifestations of each type of porphyria along with timely implementation of appropriate tests can significantly assist in the diagnosis of these rare diseases.

A Case of Erythropoietic Protoporphyria

A 53-year-old Texas rancher developed a blistering skin rash that was sensitive to exposure to sunlight. He was referred to hematology with a presumptive diagnosis of porphyria. His peripheral blood counts were within normal limits, and a bone marrow examination revealed erythroid dyspoiesis and ringed sideroblasts. Serum, plasma, and erythrocyte protoporphyrin levels were elevated, the findings of which are consistent with a diagnosis of erythropoietic protoporphyria. This paper discusses the diagnosis and etiology of the porphyrias.

Acute Intermittent Porphyria: A Diagnostic Challenge.

Porphyrias refer to a group of rare inherited metabolic disorders resulting from reduced activity of any of the enzymes in the heme production pathway. Accumulation of the porphyrin precursors is associated with diverse pathologic changes, and become the basis for diagnostic tests (1). Acute intermittent porphyria (AIP) is the most common type of porphyrias, and seizures are typically a manifestation of acute attacks. AIP can also be associated with idiopathic or symptomatic epilepsy (2). Since many antiepileptic drugs can worsen the patient’s condition or disease attacks, knowledge of the effects of AEDs is important. Trying to treat seizures may unmask AIP, which has been previously hidden. Due to the broad spectrum of clinical symptoms, porphyry diagnosis depends on a strong clinical suspicion (3). We present here a child with the final diagnosis of porphyria.

The Challenging Case of a Patient With Recurrent Unexplained Abdominal Pain: A Journey Through Cronhʼs, Porphyria, Nephrolithiasis, Shingles, and Other Zebras

We present a patient with recurrent abdominal pain and a challenging journey to find an answer to his debilitating symptoms. Through years of struggling with pain and diagnostic dilemmas, we were faced with a history of appendectomy, cholecystectomy, episodes of pancreatitis, nephrolithiasis, abdominal shingles, Crohn's disease, concern for drug seeking behavior, Irritable Bowel Syndrome, depression, recurrent hospitalizations, multiple colonoscopies, innumerable negative stool studies, a rare diagnosis of porphyria (but not the abdominal pain causing type), and finally, this arduous chase yielded a diagnosis of eosinophilic enterocolitis, another rare disease. 36 year old male with history of Crohn's disease, multiple hospitalizations for abdominal pain, cholecystectomy, and appendectomy was admitted for yet another recurrence of abdominal pain and worsening of chronic diarrhea. Objective diagnostic work-up, including an abdominal CT and other bloodwork, did not show supportive evidence for Crohn's flare. Tenderness on light touch and multiple requests for Dilaudid alerted the medical team for drug seeking behavior. However, other objective findings triggered a broader differential: a low MCV without anemia, elevated iron with normal ferritin, dark urine, history of recurring photosensitivity facial rash, a clean record on Eforcse, and the patient's long journey to find an answer for his gastrointestinal disturbances. On further review of outside records: a series of panendoscopies with no major findings, intestinal biopsies showing intermittent signs of diffuse chronic inflammation, extensive testing for chronic diarrhea, cholecystectomy of a non-inflamed and acalculous gallbladder, appendectomy, abdominal shingles, pancreatitis, nephrolithiasis and multiple frustrated doctor's notes, the answer to our enigma was thought to be found in the form of a positive porphyria work up! However, the test for acute exacerbation returned with undetectable porphyrin levels while the patient continued to be symptomatic. Despite our current disappointment, the diagnosis of porphyria was confirmed reliably at two different occasions in the past, with testing to rule-out other causes of elevated porphyrins and a pathologist interpretation of Porphyria Cutanea Tarda. In the quest to uncover the etiology to his chronic abdominal pain, porphyria was found, but not the kind that presents with abdominal pain. In the meantime, the pathology report from panendoscopy returned with findings consistent with eosinophilic enterocolitis; another rare disease, but one that finally explained his current symptoms. After ruling out celiac disease, patient was started on food elimination diet to identify trigger foods since the major cause of eosinophilic enterocolitis is food sensitivity.

Porphyria: Pathophysiology, diagnosis, and treatment.

Porphyrias are inherited metabolic disorders that involve alterations in enzymes utilized in the heme biosynthetic pathway. Most of these conditions are inherited; however, some are believed to be acquired through environmental exposures. Patients with porhyrias often present with a wide range of clinical symptoms, making it difficult to diagnose. Treatments vary depending on clinical presentation. A thorough and detailed history is essential and key to discovering a porphyria diagnosis.

Acute Porphyrias

BackgroundPorphyrias are a group of eight metabolic disorders characterized by defects in heme biosynthesis. Porphyrias are classified into two major categories: 1) the acute or inducible porphyrias and 2) the chronic cutaneous porphyrias. The acute hepatic porphyrias are further classified into acute intermittent porphyria (AIP), hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of delta-aminolevulinic acid (ALA) dehydratase (ALADP). DiscussionAIP is the most common, and ALADP is the least common acute porphyria. The clinical presentations of acute porphyrias are nonspecific. There are no pathognomonic signs or symptoms. The most frequent presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. Hyponatremia is the most common electrolyte abnormality during acute attacks, and hypomagnesemia is also common. Both are risk factors for development of seizures, which occur in ∼ 20–30% of acute attacks. ConclusionOnce suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality. Acute attacks last a few days, and the majority of patients are asymptomatic between attacks. Prognosis is good if the condition is recognized early and treated aggressively.

Acute Porphyrias in the USA: Features of 108 Subjects from Porphyrias Consortium

BackgroundRecent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects. MethodsBetween September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US. ResultsMost subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. ConclusionsAcute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.

EPA-1810 – Othello syndrome and porphyria: A clinical report

Twenty five year old man, diagnosed with porphyria. No psychiatric history until 6 months prior to the first psychiatric consult, when symptomatic anxiety in reaction to suspicious about his girlfriend's fidelity occurs. Never having arisen such suspicions during the relationship's previous years. When questioned, the pacient was unable to identify a specific event that triggered the distrust, merely reporting unfounded doubts which manifested in the form of intrusive ideas, more frequent and intense when he was alone and unoccupied. The existence of psychiatric symptomatology associated with this pathology is documented in the literature. The goal of this paper is to present a case of Otelo syndrome in a pacient with a previous diagnosis of porphyria. We aim to show the patient's psychiatric symptoms’ evolution after the diagnosis and pharmacological and psychotherapeutic treatment, discussing the therapeutic difficulties determined by clinical co-morbidity.

Diagnosis of feline acute intermittent porphyria presenting with erythrodontia requires molecular analyses

Erythrodontia is the hallmark of human congenital erythropoietic porphyria (CEP), but is also a major phenotypic feature of acute intermittent porphyria (AIP) in cats. In this study, detailed biochemical and molecular analyses were performed on two unrelated cats with autosomal dominant AIP that presented with erythrodontia, yellow–brown urine and mild changes in erythrocytes. The cats had elevated concentrations of urinary 5-aminolevulinic acid and porphobilinogen, and half normal erythrocytic hydroxymethylbilane synthase (HMBS) activity. Two novel HMBS mutations were detected; one cat had a deletion (c.107_110delACAG) and one cat had a splicing alteration (c.826-1G>A), both leading to premature stop codons and truncated proteins (p.D36Vfs∗6 and p.L276Efs∗6, respectively). These studies highlight the importance of appropriate biochemical and molecular genetic analyses for the accurate diagnoses of porphyrias in cats and extend the molecular genetic heterogeneity of feline AIP. Thus, although erythrodontia is a classic sign of congenital erythropoietic porphyria in human beings, cats with erythrodontia may have acute intermittent porphyria, a hepatic porphyria.

Leukocytoclastic vasculitis masking chronic vascular changes in previously undiagnosed erythropoietic protoporphyria

A 31-year old man presented with swelling and purpura of the dorsum of the hands following sun exposure. There was a preceding lifelong history of photosensitivity, but this episode, which occurred after the recent commencement of oral iron therapy, and after recent alcohol ingestion, was much more severe than any preceding episode. Skin biopsy performed 48 h after the onset of symptoms showed features consistent with the early stages of leukocytoclastic vasculitis. Direct immunofluorescence showed homogeneous thick staining of the vessel walls with IgG, IgM and IgA, together with abundant perivascular fibrinogen. A subsequent periodic acid-Schiff (PAS) stain on the skin biopsy revealed thickening of the walls of dermal vessels, which was not discernible in routinely stained (hematoxylin/eosin) sections. The diagnosis of erythropoietic protoporphyria (EPP) was confirmed by significantly elevated erythrocyte protoporphyrin levels and positive plasma fluorimetry. The diagnosis of porphyria may have been missed by routine skin microscopy if not for the additional information provided by clinical history, direct immunofluorescence and PAS stain. The pathogenesis and histopathology of acute and chronic vascular changes in EPP are reviewed.

19-year-old female with abdominal pain

Porphyria is a group of at least 8 diseases that differ greatly between them. Common feature of these diseases is the accumulation in the body of porphyrins or porphyrin precursors, due to defects of specific enzymes in the biosynthesis of hem. Many symptoms of porphyria are nonspecific and therefore the diagnosis is often delayed. Laboratory tests can confirm or exclude the diagnosis of porphyria. However, certain diagnosis requires demonstration of specific enzyme deficiency. The presented case demonstrates the difficulty in diagnosis of acute intermittent porphyria (AIP) in a young woman without a history of significant pathology.

A Right Royal Porphyria Fallacy

To the Editor: We were intrigued by the cover image for the November 2011 issue of Clinical Chemistry , which showed a cover picture claiming that Mary Queen of Scots had a diagnosis of acute porphyria. The diagnosis of porphyria is usually assigned when a presenting patient is currently symptomatic; the range of indicative symptoms is diverse but relatively well defined. The 3 most common acute porphyrias are hereditary coproporphyria, variegate porphyria, and acute intermittent porphyria, all inherited as autosomal dominant disorders. Many individuals who inherit the enzyme abnormalities remain asymptomatic through out life. Abdominal pain is the most common symptom of an …

Travelling wave ion mobility mass spectrometry of 5‐aminolaevulinic acid, porphobilinogen and porphyrins

Human porphyrias, diseases caused by enzyme defects in haem biosynthesis, are characterised by the excessive production, accumulation and excretion of porphyrins and/or 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). A method for the simultaneous separation, detection and identification of ALA, PBG and porphyrins would greatly facilitate the screening and diagnosis of porphyrias. Such a method would also be invaluable for the biochemical study of the haem, chlorophyll and corrin pathways. An aqueous mixture containing ALA, PBG and type I isomer porphyrins was diluted with acetonitrile and infused (10 μL/min) into a Waters Synapt G2 high-definition mass spectrometer, equipped with a Z-Spray electrospray ionisation (ESI) source. Mass spectra were acquired in positive ionisation mode and the optimised ion mobility spectrometry (IMS) conditions were as follows: IMS wave height (V), 40; IMS wave velocity (m/s), 648; IMS gas flow (mL/min) 90.40; helium gas flow (mL/min), 182.60. The IMS drift-time increased with increasing ion mass in the order of ALA, PBG, mesoporphyrin, coproporphyrin I, penta-, hexa- and heptacarboxylic acid porphyrin I and uroporphyrin I. The ESI-IMS-MS spectra shows that PBG could form two different positively charged ions by protonation [M+H](+) , m/z 227, or deprotonation [M - H](+) , m/z 225. The protonated PBG (m/z 227) easily eliminated ammonia in source and the fragment ion (m/z 210) was monitored instead. Doubly charged ions of porphyrins having different drift times from the protonated singly charged molecules were observed in high abundance, providing further structural characterisation. We have shown, for the first time, an analytical method capable of simultaneously separating haem biosynthetic intermediates and metabolites, for a potential rapid clinical screening method for the porphyrias. IMS-MS allowed the separation of doubly charged porphyrin ions, which will be advantageous for the analysis of natural and synthetic tetrapyrrole compounds, while reducing the misinterpretation of contaminants.

A novel rapid method for simultaneous determination of three diagnostically important porphyrins in erythrocytes using hyphenated synchronous fluorescence techniques

The species and concentrations of porphyrins in erythrocytes are of great importance in the clinical screening and diagnosis of porphyrias. However, it is difficult to analyze them simultaneously by conventional spectrofluorimetry. In this paper, we proposed a novel, simple and rapid method for the simultaneous determination of three diagnostically important porphyrins in human erythrocytes, protoporphyrin IX (PP), coproporphyrin III (CP) and zinc protoporphyrin IX (ZnPP), using hyphenated techniques based on derivative matrix isopotential synchronous fluorescence spectrometry and nonlinear variable-angle synchronous fluorescence spectrometry (DMI-NLVASFS). The spectral overlapping problems were well resolved and these three components were determined in one scanning without spectral compensation factors and chromatographic separation. The detection limits were 0.58, 0.21, 0.05nmolL−1 for PP, CP and ZnPP, respectively. Only 30s was needed for a single scanning and the recoveries were from 73% to 105% in erythrocytes. The Bland–Altman analysis indicates no significant difference between the proposed DMI-NLVASFS method and conventional fluorimetry method. The PP level of the erythropoietic protoporphyria (EPP) patients was significantly higher than that of healthy volunteers. This method can determine PP, CP and ZnPP simultaneously in a single scanning, thus providing a potential tool for the clinical analysis of porphyrins in human erythrocytes and the differential diagnosis of porphyrias.

Porphyrins profile by high performance liquid chromatography/electrospray ionization tandem mass spectrometry for the diagnosis of porphyria

Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway. Most porphyria symptoms are nonspecific and occur intermittently; resulting frequently in missed diagnosis since the disease itself is a rare one. The aim of the study is to establish a new reliable and accurate laboratory method for separation, identification and quantitation of urinary porphyrins by liquid chromatography tandem mass spectrometry (LC/MS/MS) and thereby the diagnosis of different porphyria types for the first time in Egypt. Screening by plasma fluorescence and quantitative determination of urinary porphyrins by high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI/MS/MS) of 50 clinically suspected patients revealed one case of variegate porphyria and five cases of porphyria cutanea tarda. Plasma fluorescence scanning is a simple procedure that can be used as screening test to detect porphyria patients that require quantitation of urinary porphyrins as a second step. Quantitative determination of urinary porphyrins using HPLC/ESI/MS/MS and ion mapping techniques are applicable for the differential diagnosis of porphyria types, since each type has a characteristic porphyrins excretion profile. Quantitative determination of urinary porphyrins by HPLC/ESI/MS/MS used in this study is a modification for the method Stoev et al. while ion mapping technique is a new technique invented by the research team at the Biochemical Genetics Department.

A case report : Featuring a young boy presenting with excessive hair growth & red colored urine

A four-year-old boy from a rural town in Saudi Arabia presented at the pediatric clinic at King Abdul-Aziz University Hospital complaining of hypertricosis, skin pigmentations, abdominal pain, vomiting and red urine. We discovered upon laboratory investigations, disturbed liver enzymes, elevated serum ferritin and high uroporphyrin values. The constellation of symptoms and the elevated uroporphyrin suggested the diagnosis of Porphyria. We would like to believe this is an interesting case, which demonstrates a number of combined clinical features in a child, who is the product of a first-degree consanguineous marriage.