Urinary Coproporphyrin Isomer Distribution in the Dubin-Johnson Syndrome

Koskelo, Pentti; Toivonen, Ilkka; Adlercreutz, Herman

doi:10.1093/clinchem/13.11.1006

Cited by 58 publications

(5 citation statements)

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“…A similar trend in the CP-I ratio was observed in feces (~3-fold increase). The CP-I ratios in bile and feces were almost identical in TR À rats and in patients with DJS, 20,43 suggesting that in both species CP-I predominates over CP-III excretion in bile and feces when Mrp2/MRP2 function is impaired. In contrast, the CP-I ratio in urine was lower (~2-fold or more) in TR À rats compared to patients with DJS, and~4-fold lower in WT rats compared to healthy human controls.…”

Section: Discussionmentioning

confidence: 92%

Endogenous Coproporphyrin I and III are Altered in Multidrug Resistance-Associated Protein 2-Deficient (TR−) Rats

Bezençon

Saran

Hußner

et al. 2021

Journal of Pharmaceutical Sciences

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Recent studies have focused on coproporphyrin (CP)-I and CP-III (CPs) as endogenous biomarkers for organic anion transporting polypeptides (OATPs). Previous data showed that CPs are also substrates of multidrug resistance-associated protein (MRP/Mrp) 2 and 3. This study was designed to examine the impact of loss of Mrp2 function on the routes of excretion of endogenous CPs in wild-type (WT) Wistar compared to Mrp2-deficient TR À rats. To exclude possible confounding effects of rat Oatps, the transport of CPs was investigated in Oatp-overexpressing HeLa cells. Results indicated that CPs are substrates of rodent Oatp1b2, and that CP-III is a substrate of Oatp2b1. Quantitative targeted absolute proteomic (QTAP) analysis revealed no differences in Oatps, but an expected significant increase in Mrp3 protein levels in TR À compared to WT rat livers. CP-I and CP-III concentrations measured by LC-MS/MS were elevated in TR À compared to WT rat liver, while CP-I and CP-III estimated biliary clearance was decreased 75-and 840-fold in TR À compared to WT rats, respectively. CP-III concentrations were decreased 14-fold in the feces of TR À compared to WT rats, but differences in CP-I were not significant. In summary, the disposition of CPs was markedly altered by loss of Mrp2 and increased Mrp3 function as measured in TR À rats.

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Section: Discussionmentioning

confidence: 92%

Endogenous Coproporphyrin I and III are Altered in Multidrug Resistance-Associated Protein 2-Deficient (TR−) Rats

Bezençon

Saran

Hußner

et al. 2021

Journal of Pharmaceutical Sciences

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“…Like bilirubin, it is eliminated via the MRP2 transporter from hepatocytes into biliary canaliculi (7). In DJS, the defect of this transporter forces the relatively hydrophobic coproporphyrin into the urinary tract (8,9). In healthy infants, coproporphyrin isomer I accounts for 66%, 44%, and 40% after birth, at age 3 and at 6 months, respectively, of total coproporphyrin, whereas coproporphyrin isomer III accounts for 34%, 56%, and 60% of total coproporphyrin at these time points (6) (Fig.…”

Section: Figurementioning

confidence: 99%

Dubin-Johnson Syndrome as Differential Diagnosis for Neonatal Cholestasis

Junge¹,

Goldschmidt²,

Wiegandt³

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder in which multidrug-resistance-associated protein 2 (MRP2) deficiency causes an excretion disorder of conjugated bilirubin from hepatocytes into bile canaliculi. Its clinical presentation as neonatal cholestasis (NC) is rare but represents an important differential diagnosis. We aimed to define DJS-specific characteristics in NC, in particular in contrast to biliary atresia (BA) patients, and to highlight diagnostic tools that can help to avoid invasive diagnostic tests. Methods: We performed a review of case records from 2006 to 2020 and compared 4 DJS patients to 26 patients with proven BA consecutively diagnosed from 2014 to 2017. DJS was diagnosed by urine coproporphyrin analysis (UCA) and by genetic analysis (GA) for disease-associated ABCC2 variants. Results: Four male patients with NC were diagnosed with DJS by UCA and GA. DJS patients presenting as NC showed significantly lower values for aspartate aminotransferase (AST) (P < 0.001), for alanine aminotransferase (ALT) (P ¼ 0.002) and for gamma-glutamyl transferase (GGT) (P < 0.001) compared with BA patients. Other examinations, however, could not clearly discriminate them (e.g.: stool colour, serum bile acids, total serum bilirubin). Conclusions: DJS is not only a rare differential diagnosis in NC with a suspicious phenotype (almost normal AST, ALT) but also shows overlapping features with BA. It should, therefore, be considered in every infant with NC and an atypical liver enzyme pattern to protect patients from unnecessary, invasive examinations. For this, UCA is a fast and reliable diagnostic tool. Confirmation based on GA is recommended. DJS patients have a good long-term prognosis.

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“…There is a marked decrease in the proportion of urinary coproporphyrin (UCP) III in total UCP in Dubin-Johnson syndrome, a disease that causes constitutional hyperbilirubinemia. 1 This means that the ratio of UCP I to the total urinary UCP I and III [UCP {I/(I + III)}] is high in Dubin-Johnson syndrome, therefore this ratio is used for auxiliary diagnosis. UCP [I/(I + III)] is approximately 0.3 in healthy adults, but it rises to ≥0.8in Dubin-Johnson syndrome patients.…”

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confidence: 99%