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neonatal citrin deficiency


Tuesday 9 March 2010

Citrin deficiency is an autosomal recessive disorder caused by mutation in the SLC25AJ3 gene.

It has two major phenotypes:
- adult-onset type II citrullinemia (CTLN2)
- neonatal intrahepatic cholestatic caused by citrin deficiency (NICCD).

NICCD is characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with multiple amino acidemia and hypergalactosemia.

NICCD is self-limiting in most patients. However, some patients may develop CTLN2 years later, which manifests as fatal hyperammonemia coma.

NICCD should be considered in the differential diagnosis of neonatal cholestatic jaundice.


- neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)

  • fibrosis
  • inflammation varied among the specimens
  • moderate or severe inflammatory changes
  • fat deposition in hepatocytes
  • severe fatty liver (67%)
  • mixture of two types of hepatocytes with macrovesicular or microvesicular fat droplets
  • cholestasis (77%)
  • hemosiderin deposition, mostly mild and localized in periportal hepatocytes and macrophages in portal areas (57%)

A combination of mixed macrovesicular and microvesicular fatty hepatocytes and findings as fatty liver, cholestasis, necroinflammatory reaction and iron deposition, are almost never observed in other liver diseases in infants and adults. NICCD is a disease with characteristic hepatopathological features. (20070398)

See also

- citrin deficiency

  • neonatal citrin deficiency
  • adult-type citrin deficiency


- Histological findings in the livers of patients with neonatal intrahepatic cholestasis caused by citrin deficiency. Kimura A, Kage M, Nagata I, Mushiake S, Ohura T, Tazawa Y, Maisawa S, Tomomasa T, Abukawa D, Okano Y, Sumazaki R, Takayanagi M, Tamamori A, Yorifuji T, Yamato Y, Maeda K, Matsushita M, Matsuishi T, Tanikawa K, Kobayashi K, Saheki T. Hepatol Res. 2010 Jan 11. PMID: 20070398

- Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK. Hutchin T, Preece MA, Hendriksz C, Chakrapani A, McClelland V, Okumura F, Song YZ, Iijima M, Kobayashi K, Saheki T, McKiernan P, Baumann U. J Inherit Metab Dis. 2009 Jun 11. PMID: 19517266

- Liver transplantation for an infant with neonatal intrahepatic cholestasis caused by citrin deficiency using heterozygote living donor. Shigeta T, Kasahara M, Kimura T, Fukuda A, Sasaki K, Arai K, Nakagawa A, Nakagawa S, Kobayashi K, Soneda S, Kitagawa H. Pediatr Transplant. 2009 Apr 3. PMID: 19413723

- Citrin deficiency, a perplexing global disorder. Dimmock D, Maranda B, Dionisi-Vici C, Wang J, Kleppe S, Fiermonte G, Bai R, Hainline B, Hamosh A, O’Brien WE, Scaglia F, Wong LJ. Mol Genet Metab. 2009 Jan;96(1):44-9. PMID: 19036621

- Chubby face and the biochemical parameters for the early diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency. Chen HW, Chen HL, Ni YH, Lee NC, Chien YH, Hwu WL, Huang YT, Chiu PC, Chang MH. J Pediatr Gastroenterol Nutr. 2008 Aug;47(2):187-92. PMID: 18664871