[2174] Neonatal Intrahepatic Cholestasis Associated with Citrin Deficiency (NICCD)

John Hicks, Heuy-Ling Chen, Yung-Ming Jeng, Mei-Hwei Chang. Texas Children's Hospital & Baylor College of Medicine, Houston, TX; National Taiwan University Hospital, Taipei, Taiwan

Background: Citrin, a mitochondrial inner membrane protein, functions as a calcium binding-stimulated aspartate-glutamate carrier component in nicotinamide adenine dinucleotide (NADH) shuttle. It is mainly expressed in the liver and participates in metabolic pathways (aerobic glycolysis, gluconeogenesis, urea cycle, protein/nucleotide synthesis). Citrin deficiency results in transient neonatal intrahepatic cholestasis (NICCD, recessive inheritance, Asian predilection). NICCD is characterized by prolonged cholestatic jaundice, low birthweight, growth retardation, hypoproteinemia, coagulopathy, anemia, hepatomegaly, liver dysfunction and hypoglycemia. Most undergo resolution by 1yr of age with appropriate treatment. Some have progressive liver disease requiring transplantation.
Design: Archives at National Taiwan University Hospital, following IRB, institutional and Department of Health approval, identified 9 neonates with genetically confirmed NICCD over a 16yr period. These neonates underwent liver biopsy and tissue was available for light and electron microscopic examination.
Results: NICCD liver biopsies showed variable degrees of cytoplasmic and canalicular cholestasis. Hepatocytes were arranged in pseudoacinar pattern. Diffuse microvesicular and macrovesicular steatosis involved vast majority of hepatocytes. Ballooning of hepatocytes was present; however apoptotic bodies were rare. Infrequent hepatocytes had undergone giant cell transformation. Occasional islands of extramedullary hematopoiesis were seen. The portal areas had mild increases in chronic inflammatory cells with no fibrosis and no bile duct proliferation. Central veins showed mild perivenule chronic inflammation. No viral cytopathic effect was seen. Electron microscopy showed hepatocytes with numerous lipid droplets of variable size. Some lipid droplets displaced and indented nuclei. Mitochondria tended to be small ovoid to slightly elongated with thick dense cristae, and not increased in numbers. Crystalline cristae were not seen. Intracytoplasmic bile was readily identified as dense aggregates. Typical peroxisome and glycogen particles were present. No viral inclusions were seen.
Conclusions: Neonatal intrahepatic cholestasis associated with citrin leads to marked lipid accumulation in hepatocytes with accumulation of intracytoplasmic bile profiles. NICCD in neonates and infants with jaundice should be a consideration in the differential diagnosis of cholestatic hepatitis with steatosis, especially in those with Asian descent.
Category: Ultrastructural

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 316, Wednesday Morning

 

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