Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK
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DOI：
10.1007/s10545-009-1116-x
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Baumann, U.
中科院分区：
文献类型：
--
作者：
Hutchin, T.;Preece, M. A.;Baumann, U.
瓜氨酸缺乏症是一种具有两种表型的疾病：由瓜氨酸缺乏症引起的新生儿肝内胆汁淤积症（NICCD）和成人发作的II型瓜氨酸血症（CTLN 2）。NICCD在出生后最初几周内表现为胆汁淤积延长和代谢异常，包括氨基酸血症（特别是瓜氨酸、酪氨酸、苏氨酸、精氨酸和蛋氨酸）和半乳糖尿。症状在出生后第一年内消退，因此在此之后很难诊断。尽管患者随后保持总体健康，但一些患者可能在一个或多个十年后出现更严重的CTLN 2症状，其特征在于神经系统变化。迄今为止，已报告了400多起病例，几乎全部来自东亚（主要是日本）。在这里，我们描述了前两例NICCD的婴儿来自英国，一个白人的起源和巴基斯坦的起源。两者都表现出典型的临床和生化变化，并通过SLC25A13基因中先前未报告的突变的存在证实了诊断。在其他种族中存在柠檬酸缺乏症意味着在诊断任何不明原因胆汁淤积的新生儿时需要考虑NICCD。我们讨论了在很少有DNA突变的人群中诊断这些患者的困难和这些患者的管理所面临的问题。这些发现也提高了尚未诊断的CTLN 2成人的可能性。
Citrin deficiency is a disorder with two phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and adult-onset type II citrullinaemia (CTLN2). NICCD presents in the first few weeks of life with prolonged cholestasis and metabolic abnormalities including aminoacidaemia (notably citrulline, tyrosine, threonine, arginine and methionine) and galactosuria. Symptoms resolve within the first year of life, thus making a diagnosis difficult after this time. Although patients subsequently remain generally healthy, some may develop more severe symptoms of CTLN2, characterized by neurological changes, one or more decades later. To date more than 400 cases have been reported, almost all from East Asia (mainly Japan). Here we describe the first two cases of NICCD in infants from the UK, one of caucasian origin and one of Pakistani origin. Both showed typical clinical and biochemical changes with a diagnosis confirmed by the presence of previously unreported mutations in the SLC25A13 gene. The presence of citrin deficiency in other ethnic groups means that NICCD needs to be considered in the diagnosis of any neonate with an unexplained cholestasis. We discuss both the difficulties in diagnosing these patients in populations where very few DNA mutations have been identified and the problems faced in the management of these patients. These findings also raise the possibility of adults with CTLN2 in whom a diagnosis has yet to be made.