Urinary Porphyrin Research Articles

Status of urinary porphyrins among population exposed to arsenic contaminated drinking water in arsenic endemic area of West Bengal, India

Status of urinary porphyrins among population exposed to arsenic contaminated drinking water in arsenic endemic area of West Bengal, India

Status of urinary porphyrins and inverse correlation of porphyrins with serum B vitamins in arsenic endemic area of West Bengal, India

Status of urinary porphyrins and inverse correlation of porphyrins with serum B vitamins in arsenic endemic area of West Bengal, India

Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity

Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01–30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses. TCDD dose-dependently repressed hepatic expression of hepcidin (Hamp and Hamp2), the master regulator of systemic Fe homeostasis, resulting in a 2.6-fold increase in serum Fe with accumulating Fe spilling into urine. Total hepatic Fe levels were negligibly increased while transferrin saturation remained unchanged. Furthermore, TCDD elicited dose-dependent gene expression changes in heme biosynthesis including the induction of aminolevulinic acid synthase 1 (Alas1) and repression of uroporphyrinogen decarboxylase (Urod), leading to a 50% increase in hepatic hemin and a 13.2-fold increase in total urinary porphyrins. Consistent with this heme accumulation, differential gene expression suggests that heme activated BACH1 and REV-ERBα/β, causing induction of heme oxygenase 1 (Hmox1) and repression of fatty acid biosynthesis, respectively. Collectively, these results suggest that Hamp repression, Fe accumulation, and increased heme levels converge to promote oxidative stress and the progression of TCDD-elicited hepatotoxicity.

Human bio-monitoring study around a plant that recycles and refines precious metals in Central Italy.

In an area characterized by the presence of a plant that recycles and refines precious metals the study aims to evaluate the exposure to the plant emissions of the residents in the neighbourhood using human urinary biomarkers, in comparison with those obtained in a reference and in an urban area and with the data concerning dispersions of plant emissions obtained through a specific diffusional model. 153 subjects in the study area, 95 in the urban area and 55 in the reference area, aged 18-60years, answered to a self-administered questionnaire and collected their 24-h urine. Urinary concentrations of antimony, silver, cadmium, cobalt, chromium, mercury, nickel, platinum, creatinine, and the porphyrin patterns were detected. The results for the 3 areas were compared using parametric and non-parametric tests. Significant higher concentrations of mercury, cadmium, silver and nickel are observed in the study area in comparison with the reference area, but no differential distribution was observed by different levels of environmental pollution defined by the study's diffusion model, and no correlation was found between the concentrations of altered urinary porphyrin and metals. Life styles being equal, residents in the study area as well as residents in the urban area have high urinary levels of mercury, silver and nickel in comparison with the reference area, suggesting common environmental pressures probably related to diffuse gold processing activities, suggesting common environmental pressures. The excess of cadmium only in the study area suggests a role played by exposure to plant emissions, even if a differential distribution was not observed by different levels of environmental pollution.

Best practice guidelines on first-line laboratory testing for porphyria.

The porphyrias are disorders of haem biosynthesis which present with acute neurovisceral attacks or disorders of sun-exposed skin. Acute attacks occur mainly in adults and comprise severe abdominal pain, nausea, vomiting, autonomic disturbance, central nervous system involvement and peripheral motor neuropathy. Cutaneous porphyrias can be acute or chronic presenting at various ages. Timely diagnosis depends on clinical suspicion leading to referral of appropriate samples for screening by reliable biochemical methods. All samples should be protected from light. Investigation for an acute attack: • Porphobilinogen (PBG) quantitation in a random urine sample collected during symptoms. Urine concentration must be assessed by measuring creatinine, and a repeat requested if urine creatinine <2 mmol/L. • Urgent porphobilinogen testing should be available within 24 h of sample receipt at the local laboratory. Urine porphyrin excretion (TUP) should subsequently be measured on this urine. • Urine porphobilinogen should be measured using a validated quantitative ion-exchange resin-based method or LC-MS. • Increased urine porphobilinogen excretion requires confirmatory testing and clinical advice from the National Acute Porphyria Service. • Identification of individual acute porphyrias requires analysis of urine, plasma and faecal porphyrins. Investigation for cutaneous porphyria: • An EDTA blood sample for plasma porphyrin fluorescence emission spectroscopy and random urine sample for TUP. • Whole blood for porphyrin analysis is essential to identify protoporphyria. • Faeces need only be collected, if first-line tests are positive or if clinical symptoms persist. Investigation for latent porphyria or family history: • Contact a specialist porphyria laboratory for advice. Clinical, family details are usually required.

A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen.

ABSTRACTA genome-wide ethyl-N-nitrosourea (ENU) mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here, we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX). A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red blood cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared with that of wild-type littermates, particularly coproporphyrinogen III, whereas males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.

Urinary Porphyrin Profile as Early Biomarker vis-a-vis Malonaldehyde as Oxidative Stress Indicator in Arsenic Exposed Individuals, West Bengal, India

Urinary Porphyrin Profile as Early Biomarker vis-a-vis Malonaldehyde as Oxidative Stress Indicator in Arsenic Exposed Individuals, West Bengal, India

Porphyria Cutanea Tarda is a Biochemical and Not Histological Diagnosis

Porphyria cutanea tarda is the most common porphyria, due to acquired deficiency of hepatic uroporphyrinogen decarboxylase (UROD) enzyme, presenting with photosensitivity and blistering skin lesions. Factors making an individual susceptible to PCT include alcohol consumption, smoking, hepatitis C, HIV, estrogen use, and UROD mutation. Diagnosis of PCT is made with typical porphyrin profile of elevated plasma porphyrins (maximum fluorescence at 620 nm) and urine porphyrins (predominant hexa-, penta-, hepta- carboxyporphyrins). Skin biopsy may show features consistent with PCT, however by themselves may not be diagnostic. PCT is readily treatable with either phlebotomy schedule or low dose hydroxychloroquine regimen. We present two cases referred to our centre, all of them diagnosed with PCT based on a skin biopsy. An 81 year old man presented with blistering skin lesions and photosensitivity on dorsal hands and scalp. Skin biopsy from dorsal hand performed by his dermatologist showed dilated blood vessels in dermis with collagen deposition, consistent with PCT. He had no susceptibility factors for PCT. The porphyrin profile was normal with plasma porphyrins of 0.1 mcg/dl (normal <0.9) and urine porphyrins of 35 nmol/L (normal <300). A 28 year old female was diagnosed with PCT based on skin biopsy. She had 4 year history of photosensitivity and plaque like lesions on dorsal hands, which were progressive in spite of being treated with hydroxychloroquine. Except history of smoking, she had no other susceptibility factors of PCT. Biochemical porphyrin profile was normal. She is being treated for pseudoporphyria secondary to doxycycline and is doing well. Conclusions: Biochemical porphyrin profile and not skin histology is the confirmatory test for the diagnosis of PCT

Hepatic porphyria: A narrative review.

Porphyrias are a group of metabolic disorders, which result from a specific abnormality in one of the eight enzymes of the heme biosynthetic pathway. These have been subdivided based on the predominant site of enzyme defect into hepatic and erythropoietic types and based on clinical presentation into acute neurovisceral and cutaneous blistering porphyrias. This review focuses on hepatic porphyrias, which include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), aminolevulinic acid dehydratase deficiency porphyria (ADP), and porphyria cutanea tarda (PCT). Of these, AIP and ADP are classified as acute porphyria, PCT as cutaneous, while VP and HCP present with both acute and cutaneous clinical manifestations. Porphobilinogen levels in a spot urine sample is the initial screening test for the diagnosis of acute hepatic porphyria, and plasma with spot urine porphyrin levels is the initial screening test to approach patients suspected of cutaneous porphyria. Specific biochemical porphyrin profile for each porphyria helps in determining the specific diagnosis. Pain relief and elimination of triggering agents are the initial steps in managing a patient presenting with an acute attack. Intravenous glucose administration terminates the mild episode of acute porphyria, with intravenous hemin needed for management of moderate to severe episodes. Liver transplantation is curative and may be needed for patients with a life-threatening acute porphyria attack or for patients with recurrent acute attacks refractory to prophylactic treatment. Of the cutaneous porphyrias, PCT is the most common and is frequently associated with a combination of multiple susceptibility factors such as alcohol use, smoking, hepatitis C virus infection, HIV infection, estrogen use, and mutations of the hemochromatosis gene. Regular phlebotomy schedule and low-dose hydroxychloroquine are effective and safe treatment options for management of PCT.

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.

Abdominal Epilepsy: A Rare Cause of Paroxysmal Abdominal Symptoms Associated with Epilepsy

INTRODUCTION: Abdominal epilepsy is an uncommon disorder in which gastrointestinal symptoms, most commonly abdominal pain result from seizure activity. It is characterized by 1) otherwise unexplained, paroxysmal gastrointestinal symptoms, 2) CNS symptoms consistent with epilepsy, 3) an abnormal electroencephalogram with findings specific for a seizure disorder and 4) improvement with anticonvulsant medication. We present a case of abdominal epilepsy in a patient with history of Temporal lobe seizure disorder. CASE: A 56 year old man presented with episodes of lower abdominal pain for 6-7 months, lasting for seconds to minutes, not associated with meals, nausea, vomiting or blood in stool. His past medical history included temporal lobe epilepsy and psoriatic arthritis. He reported neurologic symptoms preceding abdominal pain characterized by feelings of disconnect, seeing surreal colors and feeling Deja-vu. Physical exam, including vitals was normal. Lab studies showed normal CBC, CMP and FIT test. Urine porphyrin test was negative. Video EEG during the time of presentation with similar complaints showed seizure activity in the temporal lobe confirming the diagnosis of abdominal epilepsy. His medication was switched from levetiracetam to lamotrigine which improved his symptoms. DISCUSSION: Abdominal epilepsy is a rare disease in which gastrointestinal symptoms result from seizure activity. Manifestations include recurrent abdominal pain, nausea, vomiting and bloating associated with diverse CNS symptoms like confusion, fatigue, headache, dizziness and syncope. Differential diagnoses include other causes of paroxysmal gastrointestinal symptoms, such as porphyria, familial Mediterranean fever, cyclical vomiting syndrome and abdominal migraine. In patients with abdominal symptoms and headache, it is often difficult to differentiate abdominal migraine from abdominal epilepsy. An EEG is a simple, non-invasive approach to differentiate between these two entities. Patients with abdominal epilepsy usually have specific EEG abnormalities, particularly of a temporal lobe seizure disorder. Once the diagnosis is confirmed, treatment is focused on controlling the seizures. The prognosis is good with usually a dramatic response to anti-epileptic medication. KEY WORDS: Abdominal pain, Seizure, Temporal lobe epilepsy.

Hydroxychloroquine Induced Liver Injury

Introduction: Hydroxychloroquine is a commonly prescribed medication with antimalarial and anti-inflammatory properties. Drug induced liver injury is a very rarely reported side effect of this medication. Case Report: 62 year old female with history of rheumatoid arthritis, on long term prednisone, presented to the ER with 2 days of arthralgia, generalized weakness, sweats and fever up to 104F. Chest x-ray and CT of the head showed no acute abnormalities. Upon laboratory evaluation, elevated liver function tests with AST 331 and ALT 379 were noted. Bilirubin and ALP were normal. Prothrombin time not elevated. She was admitted for possible sepsis from an unknown source and placed on empiric antibiotics. Upon review of her medications it became apparent that she had started hydroxychloroquine 16 days prior to admission. Hydroxychloroquine was stopped on hospital day 2 due to concern for drug induced liver injury. Her AST and ALT peaked at 798 and 1254, respectively on hospital day 3 and represent a 17 and 20 fold increase above the ULN. Serology tests for HAV, HBV, HCV, CMV, EBV, and HIV were nonreactive. ANA titer had increased from < 1:40 four months ago to 1:80. Anti-histone antibody, ASMA, and anti ds-DNA antibody were unremarkable. There was an increase in urine porphyrin excretion. Abdominal ultrasound showed an echogenic liver consistent with hepatic steatosis and no evidence of biliary obstruction. No growth was seen on blood cultures and antibiotics were de-escalated. AST and ALT began to trend downward on hospital day 4. Her fever had abated by hospital day 6. AST and ALT were down to 228 and 487 respectively at the time of discharge on hospital day 7. She had remained afebrile without any arthralgia at follow up appointment 10 days after discharge. AST and ALT had improved to 46 and 161 respectively. Discussion: We present this case of apparent hydroxychloroquine induced liver injury to add to the fund of knowledge of drug induced liver injuries. Based on our literature review there appears to be four previously reported cases of hydroxychloroquine induced liver injury. Hydroxychloroquine may trigger an acute worsening of porphyria cutanea tarda in susceptible individuals which could present with sudden onset of fever and marked serum enzyme elevations with increased excretion of porphyrins.

Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.

Psychiatric correlates in deficit of immunoglobulins

Introduction Many neurological, oncological and autoimmune diseases may have psychiatric symptoms; these diseases sometimes start with these symptoms, so the diagnosis may be confused and the treatment is delayed. Objective Review the relationship between the secondary immune deficiency and increased predisposition to infectious processes and the psychopathological conditions which manifest themselves in some cases in these situations. Methods A 17-year-old male patient, who began psychiatry consultations when he was 3 years old due to psychomotor delay and behavior disorders. He was diagnosed with ADHD and mild mental retardation. Medical history: Viral encephalitis; Perthes disease; recurrent urinary tract infections; intestinal giardiasis; Alport syndrome. He's being treated with aripiprazole 5mg (1/2-0-0). The patient presents an episode of perplexity, psychotic anguish, auditory hallucinations and paranoid delusion. The patient presented an infectious process with general malaise, diarrhea and vomiting during previous days. Results The patient was assessed by the Departments of internal medicine, neurology and psychiatry. A cerebral TAC, lumbar puncture, EEG and urine porphyrins were requested. The secondary immune deficiency makes the patient more vulnerable in an infectious process. Discussion The diagnosis of psychotic disorder due to medical condition may be transient or recurrent. Treating of the medical condition often gets resolution of psychosis, although the symptoms can persist in some cases. There is often a prodomo of viral syndrome weeks before the rest of symptoms appear. The differential diagnosis should be made with primary psychotic disorders, affective disorders, confusional syndromes, impulse control disorder or sleep disorders, neuroleptic malignant syndrome, serotonin syndrome and substance-induced psychotic disorders.

A skin disease, a blood disease or something in between? An exploratory focus group study of patients' experiences with porphyria cutanea tarda.

BackgroundPorphyria cutanea tarda (PCT) is characterized by fragile skin with blistering on sun-exposed areas. Symptoms typically develop in late adulthood and can be triggered by iron overload, alcohol intake, oestrogens and various liver diseases. Treatment consists of phlebotomy to reduce iron, or increasing urinary porphyrin excretion by administering chlorochin. To optimize patient care, health personnel need to understand the subjective experiences of PCT.ObjectivesTo explore the experiences of persons with PCT with regard to symptoms, treatment, follow-up and prevention of the disease.MethodsInterpretive description was used as a qualitative approach. Twenty-one participants attended three focus groups. All participants had experienced PCT symptoms during the last 5 years.ResultsParticipants' experiences varied from trivializing symptoms and fragile skin to what was described as a desperate situation, with huge blisters, skin falling off and feeling as if one was in a ‘horror movie’. For some, itching was very troublesome, preventing sleep and delaying skin healing. In managing PCT a shift in focus from skin to blood was described. PCT was perceived as a chronic and systemic disease causing a range of health problems. Strategies for preventing symptoms ranged from doing nothing to frequent controls and check-ups.ConclusionsParticipants had a systemic perception of PCT, and a tendency to attribute a range of health problems to the condition. This study adds insight into the experiences patients have with PCT.

Changes in rat urinary porphyrin profiles predict the magnitude of the neurotoxic effects induced by a mixture of lead, arsenic and manganese

The neurotoxic metals lead (Pb), arsenic (As) and manganese (Mn) are ubiquitous contaminants occurring as mixtures in environmental settings. The three metals may interfere with enzymes of the heme bioshyntetic pathway, leading to excessive porphyrin accumulation, which per se may trigger neurotoxicity. Given the multi-mechanisms associated with metal toxicity, we posited that a single biomarker is unlikely to predict neurotoxicity that is induced by a mixture of metals. Our objective was to evaluate the ability of a combination of urinary porphyrins to predict the magnitude of motor activity impairment induced by a mixture of Pb/As/Mn. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L) or Mn (10mg/kg), and the 3-metal mixture (same doses as the single metals) along with a control group. Motor activity was evaluated after the administration of the last dose and 24-hour (h) urine was also collected after the treatments. Porphyrin profiles were determined both in the urine and brain. Rats treated with the metal-mixture showed a significant decrease in motor parameters compared with controls and the single metal-treated groups. Both brain and urinary porphyrin levels, when combined and analyzed by multiple linear regressions, were predictable of motor activity (p<0.05). The magnitude of change in urinary porphyrin profiles was consistent with the greatest impairments in motor activity as determined by receiver operating characteristic (ROC) curves, with a sensitivity of 88% and a specificity of 96%. Our work strongly suggests that the use of a linear combination of urinary prophyrin levels accurately predicts the magnitude of motor impairments in rats that is induced by a mixture of Pb, As and Mn.

Levels of metals in the blood and specific porphyrins in the urine in children with autism spectrum disorders.

The aim of the present study was to determine the levels of metals in blood (zinc (Zn), copper (Cu), aluminium (Al), lead (Pb) and mercury (Hg)), as well as the specific porphyrin levels in the urine of patients with autism spectrum disorder (ASD) compared with patients with other neurological disorders. The study was performed in a group of children with ASD (N = 52, average age = 6.2years) anda control group of children with other neurological disorders (N = 22, average age = 6.6years), matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = 0.595). Measurement of metals in blood was performed by atomic absorption spectrometry, while the HPLC method via a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA). In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio. In terms of blood levels of metals, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ (2) = 6.6, df = 1, p = 0.010). Additionally, no significant difference between the groups was found in terms of uroporphyrin I, heptacarboxyporphyrin I, hexacarboxyporphyrin and pentacarboxyporphyrin I. However, the levels of coproporphyrin I and coproporphyrin III were lower in the ASD group compared to the controls. Due to observed higher Cu/Zn ratio, it is suggested to test blood levels of Zn and Cu in all autistic children and give them a Zn supplement if needed.

Isolated liver disease in a patient with DeltaF508/12TG-5T/M470V: A new face of an old disease

Isolated liver disease in a patient with DeltaF508/12TG-5T/M470V: A new face of an old disease

Simultaneous Determination of Five Porphyrins in Human Urine and Plasma Using High Performance Liquid Chromatography-Tandem Mass Spectrometry

A specific and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESIMS/MS) was developed and validated for the simultaneous quantification of porphyrins (coproporphyrin, pentacarboxylporphyrin,hexacarboxylporphyrin, heptacarboxylporphyrin, and uroporphyrin) in human plasma and urine. Acidified plasma samplesand urine samples were prepared by using liquid-liquid extraction using ethyl acetate and protein precipitation with acetonitrile,respectively. The separation was achieved onto a Synergi Fusion RP column (150 mm × 2.0 mm, 4 μm) with a gradient elutionof mobile phase A (0.1% formic acid in 2 mmol/L ammonium acetate, v/v) and mobile phase B (20% methanol in acetonitrile, v/v) at a flow rate of 450 μL/min. Porphyrins and the internal standard (IS), coproporphyrin I-15N4, were detected by a tandemmass spectrometer equipped with an electrospray ion source operating in positive ion mode. Multiple reaction monitoring(MRM) transitions of the protonated precursor ions and the related product ions were optimized to increase selectivity and sensitivity. The proposed method was validated by assessing selectivity, linearity, limit of quantification (LOQ), precision, accuracy,recovery, and stability. The calibration curves were obtained in the range of 0.1-100 nmol/L and the LOQs were estimated as0.1 nmol/L for all porphyrins. Results obtained from the validation study of porphyrins showed good accuracy, precision, recovery,and stability. Finally, the proposed method was successfully applied to clinical studies on the autism spectrum disorder(ASD) diagnosis of 203 Korean children.

Porphyria cutanea tarda mit sklerodermiformen Veränderungen und Hämochromatose

A 55-year-old woman presented with blistering on the back of her hands and shiny, thickened skin in her décolletage. Laboratory examination revealed increased urinary total and high carboxylated porphyrins and homozygosity for mutation C282Y in the HFE gene. Histopathology showed thickened collagen fibers in the presternal region. Based on these findings we made the diagnosis of porphyria cutanea tarda with pseudoscleroderma and hemochromatosis. Pseudoscleroderma is a rare complication of PCT but can also constitute the first cutaneous symptom of the disease, leading the way to diagnosis. Usually, adequate treatment of PCT with normalization of porphyrin values also results in improvement of pseudoscleroderma.