Citrin deficiency, a perplexing global disorder

David Dimmock, Bruno Maranda, Carlo Dionisi-Vici, Jing Wang, Soledad Kleppe, Giuseppe Fiermonte, Renkui Bai, Bryan Hainline, Ada Hamosh, William E. O'Brien, Fernando Scaglia, Lee Jun Wong

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Citrin deficiency, caused by mutations in SLC25A13, can present with neonatal intrahepatic cholestasis or with adult onset neuropsychiatric, hepatic and pancreatic disease. Until recently, it had been thought to be found mostly in individuals of East Asian ancestry. A key diagnostic feature has been the deficient argininosuccinate synthetase (ASS) activity (E.C. 6.3.4.5) in liver, with normal activity in skin fibroblasts. In this series we describe the clinical presentation of 10 patients referred to our laboratories for sequence analysis of the SCL25A13 gene, including several patients who presented with elevated citrulline on newborn screening. In addition to sequence analysis performed on all patients, ASS enzyme activity, citrulline incorporation and Western blot analysis for ASS and citrin were performed on skin fibroblasts if available. We have found 5 unreported mutations including two apparent founder mutations in three unrelated French-Canadian patients. In marked contrast to previous cases, these patients have a markedly reduced ASS activity in skin fibroblasts. The presence of citrin protein on Western blot in three of our cases reduces the sensitivity of a screening test based on protein immunoblotting. The finding of citrin mutations in patients of Arabic, Pakistani, French Canadian and Northern European origins supports the concept that citrin deficiency is a panethnic disease.

Original languageEnglish (US)
Pages (from-to)44-49
Number of pages6
JournalMolecular Genetics and Metabolism
Volume96
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Bipolar disorder
  • Citrullinemia
  • CTLN2
  • Hepatic steatosis
  • Intrahepatic cholestasis
  • Newborn screening
  • NICCD
  • Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Citrin deficiency, a perplexing global disorder'. Together they form a unique fingerprint.

  • Cite this

    Dimmock, D., Maranda, B., Dionisi-Vici, C., Wang, J., Kleppe, S., Fiermonte, G., Bai, R., Hainline, B., Hamosh, A., O'Brien, W. E., Scaglia, F., & Wong, L. J. (2009). Citrin deficiency, a perplexing global disorder. Molecular Genetics and Metabolism, 96(1), 44-49. https://doi.org/10.1016/j.ymgme.2008.10.007