A tribute to Keiko Kobayashi and her work on citrin deficiency.

نویسنده

  • Meow-Keong Thong
چکیده

Article history: Received 3 January 2012 Accepted 3 January 2012 Available online 10 January 2012 risky investigations in infants with neonatal cholestasis, provision of appropriate dietary management and genetic counseling, and long term health surveillance [5]. In many centers in Asia and elsewhere, NICCD is a condition to be excluded early in infants with prolonged cholestasis and this had led to a change in pediatric practice. The awareness that biochemical changesmay be absent inNICCD led to the need to develop a cost effective technique formolecular diagnosis Associate Professor Keiko Kobayashi from Kagoshima University, together with Professor Takeyori Saheki, was the pioneer in the field of research on citrin deficiency. Since hermedical graduation and subsequent obtainment of her PhD at Tokushima University, Japan, Associate Professor Kobayashi had been involved in the field of biochemistry and molecular genetics—her early interest had been in the study of the molecular mechanism on the heterogeneous distribution of argininosuccinate synthetase in the liver of type II citrullinemia in 1986 [1]. This led to further research in the 1990s culminating in the characterization of the gene involved in citrin deficiency [2]. Together with Professor Saheki and their collaborators, they identified two phenotypes of citrin deficiency: citrullinemia type II (CTLN2) andneonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) anddelineated the involvement of the aspartate–glutamate carrier for urea synthesis and maintenance of the urea cycle [3]. She and her teamhadworked on all aspects of citrin deficiency, ranging from the basic sciences to epidemiology aspects aswell as the clinical and molecular heterogeneity of the condition [4–6], development of mouse models [7] as well as formulating the treatment options for citrin deficiency [8]. Associate Professor Kobayashi and her team faced a number of challenges. First, there was a perception that citrin deficiency was found mostly in Japanese and East Asians only. However, as a result of research of this condition on a global basis, citrin deficiency is now recognized as a pan-ethnic disorder [9]. Secondly, as the biochemical changes of NICCD often normalized by 6 months of age, molecular diagnosis was the main option available for a definitive diagnosis. She received numerous requests from many developing countries, particularly from Asia who sought her help in making the molecular diagnosis of this condition. Despite many limitations, she always managed to answer her email correspondence promptly with her offers to help out. As prolonged cholestasis is a common condition in Asian infants, many babies were subjected to liver biopsy and laparotomy to exclude biliary atresia. As a result of the availability of genetic testing of the SLC25A13, this led to the earlier diagnosis of

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Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.

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عنوان ژورنال:
  • Molecular genetics and metabolism

دوره 105 4  شماره 

صفحات  -

تاریخ انتشار 2012