Beyond an obvious cause of cholestasis in a toddler: compound heterozygosity for ABCB11 mutations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00078119" target="_blank" >RIV/00023001:_____/19:00078119 - isvavai.cz</a>

Výsledek na webu

<a href="https://pediatrics.aappublications.org/content/143/5/e20182146" target="_blank" >https://pediatrics.aappublications.org/content/143/5/e20182146</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1542/peds.2018-2146" target="_blank" >10.1542/peds.2018-2146</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Beyond an obvious cause of cholestasis in a toddler: compound heterozygosity for ABCB11 mutations

Popis výsledku v původním jazyce

A 27-month-old girl with severe cholestasis, a compound heterozygote for PFIC2-associated and BRIC2-associated ABCB11 mutations, over 5 years developed cirrhosis necessitating liver transplant. A 27-month-old girl presented with a short history of jaundice initially attributed to drug-induced liver injury. During the preceding 20 days, she had received a 10-day course of cefprozil and 2 doses of a homeopathic preparation of cantharidin for cystitis. Severe conjugated hyperbilirubinemia was present with normal gamma-glutamyl transpeptidase activity. Liver biopsy revealed marked canalicular and hepatocellular cholestasis, with moderate hepatocellular disarray, as well as evidence of chronicity, including moderate portal-tract and perisinusoidal fibrosis. Immunohistochemical studies revealed that bile salt export pump expression was preserved, whereas canalicular gamma-glutamyl transpeptidase expression was largely absent. An inherited cholestatic disorder was suspected. The entire coding region of ABCB11, encoding bile salt export pump, was analyzed. The patient was found to be a compound heterozygote for the missense mutation c.3148C&gt;T (p.Arg1050Cys) associated with benign recurrent intrahepatic cholestasis type 2 in the homozygous state and for the nonsense mutation c.3904G&gt;T (p.Glu1302Ter) associated with progressive familial intrahepatic cholestasis type 2. Despite initial improvement with ursodeoxycholic acid, over the course of 5 years the patient developed cirrhosis that required liver transplant. Our report emphasizes the need for molecular studies even in patients with putatively explained cholestasis to reveal the entire spectrum of inherited cholestatic disorders.

Název v anglickém jazyce

Beyond an obvious cause of cholestasis in a toddler: compound heterozygosity for ABCB11 mutations

Popis výsledku anglicky

A 27-month-old girl with severe cholestasis, a compound heterozygote for PFIC2-associated and BRIC2-associated ABCB11 mutations, over 5 years developed cirrhosis necessitating liver transplant. A 27-month-old girl presented with a short history of jaundice initially attributed to drug-induced liver injury. During the preceding 20 days, she had received a 10-day course of cefprozil and 2 doses of a homeopathic preparation of cantharidin for cystitis. Severe conjugated hyperbilirubinemia was present with normal gamma-glutamyl transpeptidase activity. Liver biopsy revealed marked canalicular and hepatocellular cholestasis, with moderate hepatocellular disarray, as well as evidence of chronicity, including moderate portal-tract and perisinusoidal fibrosis. Immunohistochemical studies revealed that bile salt export pump expression was preserved, whereas canalicular gamma-glutamyl transpeptidase expression was largely absent. An inherited cholestatic disorder was suspected. The entire coding region of ABCB11, encoding bile salt export pump, was analyzed. The patient was found to be a compound heterozygote for the missense mutation c.3148C&gt;T (p.Arg1050Cys) associated with benign recurrent intrahepatic cholestasis type 2 in the homozygous state and for the nonsense mutation c.3904G&gt;T (p.Glu1302Ter) associated with progressive familial intrahepatic cholestasis type 2. Despite initial improvement with ursodeoxycholic acid, over the course of 5 years the patient developed cirrhosis that required liver transplant. Our report emphasizes the need for molecular studies even in patients with putatively explained cholestasis to reveal the entire spectrum of inherited cholestatic disorders.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30219 - Gastroenterology and hepatology

Projekt

<a href="/cs/project/NV18-06-00032" target="_blank" >NV18-06-00032: Molekulární příčiny a mechanismy dědičných intrahepatálních cholestáz</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pediatrics

ISSN

0031-4005

e-ISSN

—

Svazek periodika

143

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

"art. no. e20182146"

Kód UT WoS článku

000474923900007

EID výsledku v databázi Scopus

2-s2.0-85065511192