A tribute to Keiko Kobayashi and her work on citrin deficiency.
نویسنده
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
منابع مشابه
Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.
Citrin is the liver-type mitochondrial aspartate-glutamate carrier that participates in urea, protein, and nucleotide biosynthetic pathways by supplying aspartate from mitochondria to the cytosol. Citrin also plays a role in transporting cytosolic NADH reducing equivalents into mitochondria as a component of the malate-aspartate shuttle. In humans, loss-of-function mutations in the SLC25A13 gen...
متن کاملGenotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.
Citrin is a liver-type aspartate/glutamate carrier (AGC) encoded by the gene SLC25A13. Two phenotypes for human citrin deficiency have been described, namely the adult-onset citrullinemia type II (CTLN2) and the neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). However, citrin deficiency currently remains a perplexing and poorly recognized disorder. In particular, descripti...
متن کاملSix cases of citrin deficiency in Korea.
Citrin deficiency resulting from mutations of the SLC25A13 gene is associated with two major clinical phenotypes; neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type 2 citrullinemia (CTLN2). In Korea, 6 cases of citrin deficiency were diagnosed based on biochemical and molecular findings. Four NICCD patients (2 boys and 2 girls) presented high citrulline l...
متن کاملHepatocellular carcinoma in a case of adult-onset type II citrullinemia.
A 40-year-old woman was admitted with altered consciousness and hyperammonemia after she had delivered her first baby. DNA analysis of the citrin gene and enzymatic assay of argininosuccinate synthetase in the liver led to a diagnosis of adult-onset type II citrullinemia (CTLN2). She was also found to have hepatocellular carcinoma (HCC) and underwent palliative surgery consisting of partial liv...
متن کاملNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in three Malay children.
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) and 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 sel...
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ورودعنوان ژورنال:
- Molecular genetics and metabolism
دوره 105 4 شماره
صفحات -
تاریخ انتشار 2012