Citrin deficiency: A novel cause of failure to thrive that responds to a high-protein, low-carbohydrate diet
Citrin deficiency: A novel cause of failure to thrive that responds to a high-protein, low-carbohydrate diet
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DOI：
10.1542/peds.2006-1950
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发表时间：
2007-03-01
期刊：
影响因子：
8
通讯作者：
Scaglia, Fernando
中科院分区：
文献类型：
--
作者：
Dimmock, David;Kobayashi, Keiko;Scaglia, Fernando
先证者出生在36周，适合胎龄，非血缘的白色父母。新生儿期无高胆红素血症或肝内胆汁淤积的证据，新生儿筛查结果正常。她出现了3次危及生命的出血和贫血。对她的出血素质的诊断评价显示凝血异常，没有肝细胞损伤的生化证据。偶然发现她有严重的生长减速，对每天502 kJ/ kg（120 kcal/ kg）的蛋白水解配方奶粉没有反应。对发育不良进行了广泛的诊断性检查，这在其他方面是正常的，包括血浆氨基酸分析，显示高维生素A血症和瓜氨酸水平在参考范围内。重复样本检测显示孤立性高瓜氨酸血症。未检测到氨基琥珀酸。她的氨水平和尿乳清酸在参考范围内。随后的血浆氨基酸分析显示，瓜氨酸、蛋氨酸和苏氨酸升高，提示瓜氨酸缺乏引起新生儿肝内胆汁淤积。成纤维细胞的蛋白质印迹证明柠檬酸缺乏，并在患者的SLC 25 A13基因的编码DNA中发现外显子3的缺失。根据患有这种疾病的成年人的经验，给予患者高蛋白、低碳水化合物的饮食。不能茁壮成长和出血素质得到解决。当饮食处方的依从性放松时，再次注意到生长减速，尽管没有复发显著出血。这是第一次报告的婴儿北方欧洲血统与citrin缺乏症。年龄晚，表现为不能茁壮成长和出血素质，没有明显的新生儿肝内胆汁淤积症的证据，扩大了Citrin缺乏症的临床谱。这种情况下，强调了持续的饮食控制和生长监测的重要性，在新生儿肝内胆汁淤积症引起的柠檬酸缺乏症的儿童，并确定了一个新的代谢实体负责未能茁壮成长。
The proband was born at 36 weeks, appropriate for gestational age, to nonconsanguineous white parents. There was no evidence of hyperbilirubinemia or intrahepatic cholestasis in the neonatal period, and she had normal newborn screen results. She presented with 3 episodes of life- threatening bleeding and anemia. The diagnostic evaluation for her bleeding diathesis revealed an abnormal clotting profile with no biochemical evidence for hepatocellular damage. She was incidentally noted to have severe growth deceleration that failed to respond to 502 kJ/ kg ( 120 kcal/ kg) per day of protein- hydrolyzed formula. An extensive diagnostic workup for failure to thrive, which was otherwise normal, included plasma amino acid analysis that revealed hyperglutaminemia and citrulline levels within the reference range. Testing of a repeat sample revealed isolated hypercitrullinemia. No argininosuccinic acid was detected. Her ammonia level and urine orotic acid were within the reference ranges. Subsequent plasma amino acid analysis exhibited a profile suggestive of neonatal intrahepatic cholestasis caused by citrin deficiency with elevations in citrulline, methionine, and threonine. Western blotting of fibroblasts demonstrated citrin deficiency, and a deletion for exon 3 was found in the patient's coding DNA of the SLC25A13 gene. On the basis of the experience with adults carrying this condition, the patient was given a high- protein, low- carbohydrate diet. The failure to thrive and bleeding diathesis resolved. When compliance with the dietary prescription was relaxed, growth deceleration was again noted, although significant bleeding did not recur. This is the first report of an infant of Northern European descent with citrin deficiency. The later age at presentation with failure to thrive and bleeding diathesis and without obvious evidence of neonatal intrahepatic cholestasis expands the clinical spectrum of citrin deficiency. This case emphasizes the importance of continued dietary control and growth monitoring in children with neonatal intrahepatic cholestasis caused by citrin deficiency and identifies a new metabolic entity responsible for failure to thrive.