Spectrophotometric quantification of total urinary porphyrins as a screening test for porphyrias: Threshold value revisited

Wolff, Fleur; Gulbis, Béatrice; Cotton, Frédéric

doi:10.1016/j.clinbiochem.2013.08.021

Cited by 3 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TIBC values were used to calculate transferrin saturation using transferrin saturation = serum Fe/TIBC × 100%. Total porphyrins in the urine (vehicle and 30 μg/kg TCDD groups) were quantified using a modified spectrophotometric method (Wolff et al , 2013). Uroporphyrin (8-carboxyporphyrin) accounts for 90% of mouse hepatic porphyrins in TCDD-elicited porphyria (Goldstein et al , 1973) and therefore the molar absorptivity of uroporphyrin(541,000 M −1 cm −1 ) was used to calculate the concentration of total urinary porphyrins.…”

Section: Methodsmentioning

confidence: 99%

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

Fader

Nault

Kirby

et al. 2017

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

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 0.01–30 μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4 days for 28 days. 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.

show abstract

Section: Methodsmentioning

confidence: 99%

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

Fader

Nault

Kirby

et al. 2017

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

show abstract

“…In order to accurately diagnose PCT, as with other porphyrias, testing must be performed for porphyrins of the blood, urine, and feces (Table ). Spectrophotometric scanning of acidified urine is the first‐line test to screen for increased porphyrin excretion levels . Increased plasma uroporphyrin levels are seen as a 619–626 nm peak on the spectrofluorimetry, a screening test for the porphyrias at a neutral pH .…”

Section: Diagnosis Of Pctmentioning

confidence: 99%

“…Spectrophotometric scanning of acidified urine is the first‐line test to screen for increased porphyrin excretion levels . Increased plasma uroporphyrin levels are seen as a 619–626 nm peak on the spectrofluorimetry, a screening test for the porphyrias at a neutral pH . The fluorescence emission peak between 619 and 626 nm is not specific for PCT but also present in VP, HCP, and hepatic erythropoietic porphyria (HEP).…”

Section: Diagnosis Of Pctmentioning

confidence: 99%

Porphyria cutanea tarda: an intriguing genetic disease and marker

Handler

Stephany

et al. 2017

Int J Dermatology

View full text Add to dashboard Cite

Porphyrias are a group of intriguing genetic diseases of the heme pathway, of which porphyria cutanea tarda (PCT) is the most common. Resulting from a defect in enzymes in the porphyria pathway, PCT has been linked to several conditions. Recent studies have demonstrated a change in thinking regarding the human immunodeficiency virus (HIV) and development of PCT. The exacerbation of PCT with contraction of HIV is now believed to result from coinfection from the hepatitis C virus (HCV). Blistering of sun-exposed skin, a classic presenting sign of PCT, is not exclusive to the condition. Cutaneous findings must also trigger physicians to consider additional types of porphyrias, such as variegate porphyria. The diagnosis of pseudoporphyria, which does not result from enzymatic absence, must be considered in patients with photosensitivity and cutaneous bullae. Recent health food trends, such as chlorophyll, have been linked to pseudoporphyria. PCT is a serious condition in which accurate diagnosis is necessary for appropriate management.

show abstract

Practical recommendations for biochemical and genetic diagnosis of the porphyrias

Aarsand,

To‐Figueras,

Whatley

et al. 2024

Liver International

View full text Add to dashboard Cite

The porphyrias are a group of rare inborn errors of metabolism associated with various clinical presentations and long‐term complications, making them relevant differential diagnoses to consider for many clinical specialities, especially hepatologists, gastroenterologists and dermatologists. To diagnose a patient with porphyria requires appropriate biochemical investigations, as clinical features alone are not specific enough. Furthermore, it is important to be aware that abnormalities of porphyrin accumulation and excretion occur in many other disorders that are collectively far more common than the porphyrias. In this review, we provide an overview of porphyria‐related tests with their strengths and limitations, give recommendations on requesting and diagnostic approaches in non‐expert and expert laboratories for different clinical scenarios and discuss the role of genetic testing in the porphyrias. To diagnose porphyria in a currently symptomatic patient requires analysis of biochemical markers to demonstrate typical patterns of haem precursors in urine, faeces and blood. The use of genomic sequencing in diagnostic pathways for porphyrias requires careful consideration, and the demonstration of increased porphyrin‐related markers is necessary prior to genomic testing in symptomatic patients. In the acute porphyrias, genomic testing is presently a useful adjunct for genetic counselling of asymptomatic family members and the most common cutaneous porphyria, porphyria cutanea tarda, is usually a sporadic, non‐hereditary disease. Getting a correct and timely porphyria diagnosis is essential for delivering appropriate care and ensuring best patient outcome.

show abstract

Spectrophotometric quantification of total urinary porphyrins as a screening test for porphyrias: Threshold value revisited

Cited by 3 publications

References 15 publications

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

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

Porphyria cutanea tarda: an intriguing genetic disease and marker

Practical recommendations for biochemical and genetic diagnosis of the porphyrias

Contact Info

Product

Resources

About