Skip to main content
Erschienen in: Journal of Inherited Metabolic Disease 3/2010

01.12.2010 | Case Report

Neonatal intrahepatic cholestasis associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients

verfasst von: Hui Bein Chew, Lock Hock Ngu, Md Yunus Zabedah, Wee Teik Keng, Shanti Balasubramaniam, Mohd Jamil M. Hanifah, Keiko Kobayashi

Erschienen in: Journal of Inherited Metabolic Disease | Sonderheft 3/2010

Einloggen, um Zugang zu erhalten

Abstract

Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.
Literatur
Zurück zum Zitat Ben-Shalom E, Kobayashi K, Shaag A et al (2002) Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids. Mol Genet Metab 77:202–208PubMedCrossRef Ben-Shalom E, Kobayashi K, Shaag A et al (2002) Infantile citrullinemia caused by citrin deficiency with increased dibasic amino acids. Mol Genet Metab 77:202–208PubMedCrossRef
Zurück zum Zitat Dimmock DP, Kobayashi K, Iijima M et al (2007) Citrin deficiency: a novel cause of failure to thrive that responds to a high protein, low carbohydrate diet. Pediatrics 119:e773–777PubMedCrossRef Dimmock DP, Kobayashi K, Iijima M et al (2007) Citrin deficiency: a novel cause of failure to thrive that responds to a high protein, low carbohydrate diet. Pediatrics 119:e773–777PubMedCrossRef
Zurück zum Zitat Ko JM, Kim GH, Kim JH et al (2007) Six cases of citrin deficiency in Korea. Int J Mol Med 20:809–815PubMed Ko JM, Kim GH, Kim JH et al (2007) Six cases of citrin deficiency in Korea. Int J Mol Med 20:809–815PubMed
Zurück zum Zitat Kobayashi K, Sinasac DS, Iijima M et al (1999) The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet 22:159–163PubMedCrossRef Kobayashi K, Sinasac DS, Iijima M et al (1999) The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat Genet 22:159–163PubMedCrossRef
Zurück zum Zitat Luder AS, Tabata A, Iijima M, Kobayashi K, Mandel H (2006) Citrullinaemia type 2 outside East Asia: Israeli experience. J Inherit Metab Dis 29(suppl):59 Luder AS, Tabata A, Iijima M, Kobayashi K, Mandel H (2006) Citrullinaemia type 2 outside East Asia: Israeli experience. J Inherit Metab Dis 29(suppl):59
Zurück zum Zitat Ohura T, Kobayashi K, Tazawa Y et al (2007) Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). J Inherit Metab Dis 30:139–144PubMedCrossRef Ohura T, Kobayashi K, Tazawa Y et al (2007) Clinical pictures of 75 patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). J Inherit Metab Dis 30:139–144PubMedCrossRef
Zurück zum Zitat Saheki T, Kobayashi K (2002) Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet 47:333–341PubMedCrossRef Saheki T, Kobayashi K (2002) Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). J Hum Genet 47:333–341PubMedCrossRef
Zurück zum Zitat Saheki T, Kobayashi K, Iijima M et al (2002) Pathogenesis and pathophysiology of citrin (a mitochondrial aspartate glutamate carrier) deficiency. Metab Brain Dis 17(4):335–346PubMedCrossRef Saheki T, Kobayashi K, Iijima M et al (2002) Pathogenesis and pathophysiology of citrin (a mitochondrial aspartate glutamate carrier) deficiency. Metab Brain Dis 17(4):335–346PubMedCrossRef
Zurück zum Zitat Saheki T, Kobayashi K, Iijima M et al (2004) Adult-onset type II citrullinaemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab 81(suppl 1):20–26CrossRef Saheki T, Kobayashi K, Iijima M et al (2004) Adult-onset type II citrullinaemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle. Mol Genet Metab 81(suppl 1):20–26CrossRef
Zurück zum Zitat Tabata A, Sheng J-S, Ushikai M et al (2008) Identification of 13 novel mutations including a retrotransposal insertion in SLC25A13 gene and frequency of 30 mutations found in patients with citrin deficiency. J Hum Genet 53:534–545PubMedCrossRef Tabata A, Sheng J-S, Ushikai M et al (2008) Identification of 13 novel mutations including a retrotransposal insertion in SLC25A13 gene and frequency of 30 mutations found in patients with citrin deficiency. J Hum Genet 53:534–545PubMedCrossRef
Zurück zum Zitat Tamamori A, Okano Y, Ozaki H (2002) Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. Eur J Pediatr 161:609–613PubMedCrossRef Tamamori A, Okano Y, Ozaki H (2002) Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation. Eur J Pediatr 161:609–613PubMedCrossRef
Zurück zum Zitat Tamamori A, Fujimoto A, Okano Y et al (2004) Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency. Pediatr Res 56(4):608–614PubMedCrossRef Tamamori A, Fujimoto A, Okano Y et al (2004) Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency. Pediatr Res 56(4):608–614PubMedCrossRef
Zurück zum Zitat Tazawa Y, Kobayashi K, Abukawa D et al (2004) Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. Mol Genet Metab 83:213–219PubMedCrossRef Tazawa Y, Kobayashi K, Abukawa D et al (2004) Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients. Mol Genet Metab 83:213–219PubMedCrossRef
Zurück zum Zitat Tokuhara D, Iijima M, Tamamori A et al (2007) Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes. Mol Genet Metab 90:30–36PubMedCrossRef Tokuhara D, Iijima M, Tamamori A et al (2007) Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes. Mol Genet Metab 90:30–36PubMedCrossRef
Zurück zum Zitat Tomomasa T, Kobayashi K, Kaneko H et al (2001) Possible clinical and histologic manifestations of adult-onset type II citrullinaemia in early infancy. J Pediatr 138:741–743PubMedCrossRef Tomomasa T, Kobayashi K, Kaneko H et al (2001) Possible clinical and histologic manifestations of adult-onset type II citrullinaemia in early infancy. J Pediatr 138:741–743PubMedCrossRef
Zurück zum Zitat Yeh J-N, Jeng Y-M, Chen H-L, Ni Y-H, Hwu W-L, Chang M-H (2006) Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants. J Pediatr 148:642–646PubMedCrossRef Yeh J-N, Jeng Y-M, Chen H-L, Ni Y-H, Hwu W-L, Chang M-H (2006) Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants. J Pediatr 148:642–646PubMedCrossRef
Metadaten
Titel
Neonatal intrahepatic cholestasis associated with citrin deficiency (NICCD): a case series of 11 Malaysian patients
verfasst von
Hui Bein Chew
Lock Hock Ngu
Md Yunus Zabedah
Wee Teik Keng
Shanti Balasubramaniam
Mohd Jamil M. Hanifah
Keiko Kobayashi
Publikationsdatum
01.12.2010
Verlag
Springer Netherlands
Erschienen in
Journal of Inherited Metabolic Disease / Ausgabe Sonderheft 3/2010
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI
https://doi.org/10.1007/s10545-010-9248-6

Weitere Artikel der Sonderheft 3/2010

Journal of Inherited Metabolic Disease 3/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.