Porphyrins, Porphobilinogen, and δ-Aminolevulinic Acid

Minder, Elisabeth I.; Schneider‐Yin, Xiaoye

doi:10.1007/978-3-540-76698-8_33

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…PPIX and zinc protoporphyrin (ZnPP) were quantified by extraction and high-performance liquid chromatography (HPLC), as recently published (Minder and Schneider-Yin 2008). Transferrin, ferritin, iron, and hemoglobin measurements were performed in the local clinical laboratories in Zürich and Rome by standard procedures.…”

Section: Laboratory Analysesmentioning

confidence: 99%

Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity

Barman-Aksoezen

Girelli

Aurizi

et al. 2017

J of Inher Metab Disea

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Patients with erythropoietic protoporphyria (EPP) have reduced activity of the enzyme ferrochelatase that catalyzes the insertion of iron into protoporphyrin IX (PPIX) to form heme. As the result of ferrochelatase deficiency, PPIX accumulates and causes severe photosensitivity. Among different patients, the concentration of PPIX varies considerably. In addition to photosensitivity, patients frequently exhibit low serum iron and a microcytic hypochromic anemia. The aims of this study were to (1) search for factors related to PPIX concentration in EPP, and (2) characterize anemia in EPP, i.e., whether it is the result of an absolute iron deficiency or the anemia of chronic disease (ACD). Blood samples from 67 EPP patients (51 Italian and 16 Swiss) and 21 healthy volunteers were analyzed. EPP patients had lower ferritin (p = 0.021) and hepcidin (p = 0.031) concentrations and higher zinc-protoporphyrin (p < 0.0001) and soluble-transferrin-receptor (p = 0.0007) concentrations compared with controls. This indicated that anemia in EPP resulted from an absolute iron deficiency. Among EPP patients, PPIX concentrations correlated with both growth differentiation factor (GDF) 15 (p = 0.012) and male gender (p = 0.015). Among a subgroup of patients who were iron replete, hemoglobin levels were normal, which suggested that iron but not ferrochelatase is the limiting factor in heme synthesis of individuals with EPP.

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Section: Laboratory Analysesmentioning

confidence: 99%

Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity

Barman-Aksoezen

Girelli

Aurizi

et al. 2017

J of Inher Metab Disea

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“…The latter is technical standard today. Published reference intervals of urinary porphyrins based on this HPLC method are available for children [32,33] and for adults [7,20,34]. Table 3 shows the reference intervals of 24-h urine porphyrins for adults from the study of Hindmarsh et al [20] which was performed with the largest sample of the aforementioned reference interval studies (96 adults).…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of the porphyrins (uroporphyrin, hepta-, hexa-and pentacarboxy porphyrins, coproporphyrin I and III) and their precursors (δ-aminolevulinic acid and porphobilinogen) were determined by HPLC with fluorescence detection [7] and by ion-exchange chromatography with spectrophotometric detection after reaction with modified Ehrlich's reagent [8], respectively. Osmolality of the urine specimens was measured by freezing point depression (Advanced Instruments, Needham Heights, MA, USA).…”

Section: Laboratory Testsmentioning

confidence: 99%

Reference intervals for 24 laboratory parameters determined in 24-hour urine collections

Curcio

Stettler

Suter

et al. 2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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BACKGROUND: Reference intervals for many laboratory parameters determined in 24-h urine collections are either not publicly available or based on small numbers, not sex specific or not from a representative sample. METHODS: Osmolality and concentrations or enzymatic activities of sodium, potassium, chloride, glucose, creatinine, citrate, cortisol, pancreatic -amylase, total protein, albumin, transferrin, immunoglobulin G, 1-microglobulin, 2-macroglobulin, as well as porphyrins and their precursors ( -aminolevulinic acid and porphobilinogen) were determined in 241 24-h urine samples of a population-based cohort of asymptomatic adults (121 men and 120 women). For 16 of these 24 parameters creatinine-normalized ratios were calculated based on 24-h urine creatinine. The reference intervals for these parameters were calculated according to the CLSI C28-A3 statistical guidelines. RESULTS: By contrast to most published reference intervals, which do not stratify for sex, reference intervals of 12 of 24 laboratory parameters in 24-h urine collections and of eight of 16 parameters as creatininenormalized ratios differed significantly between men and women. For six parameters calculated as 24-h urine excretion and four parameters calculated as creatinine-normalized ratios no reference intervals had been published before. For some parameters we found significant and relevant deviations from previously reported reference intervals, most notably for 24-h urine cortisol in women. Ten 24-h urine parameters showed weak or moderate sex-specific correlations with age. CONCLUSIONS: By applying up-to-date analytical methods and clinical chemistry analyzers to 24-h urine collections from a large populationbased cohort we provide as yet the most comprehensive set of sex-specific reference intervals calculated according to CLSI guidelines for parameters determined in 24-h urine collections. AbstractBackground: Reference intervals for many laboratory parameters determined in 24-h urine collections are either not publicly available or based on small numbers, not sex specific or not from a representative sample. Methods: Osmolality and concentrations or enzymatic activities of sodium, potassium, chloride, glucose, creatinine, citrate, cortisol, pancreatic α-amylase, total protein, albumin, transferrin, immunoglobulin G, α 1 -microglobulin, α 2 -macroglobulin, as well as porphyrins and their precursors (δ-aminolevulinic acid and porphobilinogen) were determined in 241 24-h urine samples of a population-based cohort of asymptomatic adults (121 men and 120 women). For 16 of these 24 parameters creatininenormalized ratios were calculated based on 24-h urine creatinine. The reference intervals for these parameters were calculated according to the CLSI C28-A3 statistical guidelines. Results: By contrast to most published reference intervals, which do not stratify for sex, reference intervals of 12 of 24 laboratory parameters in 24-h urine collections and of eight of 16 parameters as creatinine-normalized ratios differed significantly...

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“…The quantification of ALA and PBG was performed using the ClinEasy ® kit (Recipe Chemicals + Instruments GmbH, Munich, Germany) from native urine samples. The differentiation and quantification of urinary and faecal porphyrins, the plasma fluorescence scan, and HMBS enzymatic activity assays were performed according to previously published methods [ 11 ]. The Swiss Reference Centre for Porphyrias is a recognized specialist centre of the Nationale Koordination Seltene Krankheiten (kosek) and the European Porphyria Network, and all the laboratory methods listed under Section 2.2 and Section 2.3 (Sanger sequencing) are accredited by the Swiss Accreditation Service (SAS), according to the ISO norm 15,189 for medical laboratories.…”

Section: Methodsmentioning

confidence: 99%

First Report of a Low-Frequency Mosaic Mutation in the Hydroxymethylbilane Synthase Gene Causing Acute Intermittent Porphyria

Belosevic,

Minder,

Gueuning

et al. 2023

Life

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Acute porphyrias are a group of monogenetic inborn errors of heme biosynthesis, characterized by acute and potentially life-threatening neurovisceral attacks upon exposure to certain triggering factors. Biochemical analyses can determine the type of acute porphyria, and subsequent genetic analysis allows for the identification of pathogenic variants in the specific gene, which provides information for family counselling. In 2017, a male Swiss patient was diagnosed with an acute porphyria while suffering from an acute attack. The pattern of porphyrin metabolite excretion in urine, faeces, and plasma was typical for an acute intermittent porphyria (AIP), which is caused by inherited autosomal dominant mutations in the gene for hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. However, the measurement of HMBS enzymatic activity in the erythrocytes was within the normal range and Sanger sequencing of the HMBS gene failed to detect any pathogenic variants. To explore the molecular basis of the apparent AIP in this patient, we performed third-generation long-read single-molecule sequencing (nanopore sequencing) on a PCR product spanning the entire HMBS gene, including the intronic sequences. We identified a known pathogenic variant, c.77G>A, p.(Arg26His), in exon 3 at an allelic frequency of ~22% in the patient’s blood. The absence of the pathogenic variant in the DNA of the parents and the results of additional confirmatory studies supported the presence of a de novo mosaic mutation. To our knowledge, such a mutation has not been previously described in any acute porphyria. Therefore, de novo mosaic mutations should be considered as potential causes of acute porphyrias when no pathogenic genetic variant can be identified through routine molecular diagnostics.

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Porphyrins, Porphobilinogen, and δ-Aminolevulinic Acid

Cited by 5 publications

References 16 publications

Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity

Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity

Reference intervals for 24 laboratory parameters determined in 24-hour urine collections

First Report of a Low-Frequency Mosaic Mutation in the Hydroxymethylbilane Synthase Gene Causing Acute Intermittent Porphyria

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