Clinical manifestation and long-term outcome of citrin deficiency: Report from a nationwide study in Japan

Jun Kido, Johannes Häberle, Keishin Sugawara, Toju Tanaka, Masayoshi Nagao, Takaaki Sawada, Yoichi Wada, Chikahiko Numakura, Kei Murayama, Yoriko Watanabe, Kanako Kojima-Ishii, Hideo Sasai, Kiyotaka Kosugiyama, Kimitoshi Nakamura

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene. The disease can present with age-dependent clinical manifestations: neonatal intrahepatic cholestasis by citrin deficiency (NICCD), failure to thrive, and dyslipidemia by citrin deficiency (FTTDCD), and adult-onset type II citrullinemia (CTLN2). As a nationwide study to investigate the clinical manifestations, medical therapy, and long-term outcome in Japanese patients with citrin deficiency, we collected clinical data of 222 patients diagnosed and/or treated at various different institutions between January 2000 and December 2019. In the entire cohort, 218 patients were alive while 4 patients (1 FTTDCD and 3 CTLN2) had died. All patients <20 years were alive. Patients with citrin deficiency had an increased risk for low weight and length at birth, and CTLN2 patients had an increased risk for growth impairment during adolescence. Liver transplantation has been performed in only 4 patients (1 NICCD, 3 CTLN2) with a good response thereafter. This study reports the diagnosis and clinical course in a large cohort of patients with citrin deficiency and suggests that early intervention including a low carbohydrate diet and MCT supplementation can be associated with improved clinical course and long-term outcome.

Original languageEnglish
Pages (from-to)431-444
Number of pages14
JournalJournal of Inherited Metabolic Disease
Issue number3
Publication statusPublished - 2022 May


  • CTLN2
  • Citrullinemia type 2
  • MCT
  • citrulline
  • long-term survival

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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