Lodoso Torrecilla B, Palomo Atance E, Camarena Grande C, Díaz Fernández Maria C, Hierro Llanillo L, De la Vega Bueno A, Frauca Remacha E, Muñoz Bartolo G, Jara Vega P
Servicio de Hepatología, Hospital Infantil Universitario La Paz, Madrid, España.
An Pediatr (Barc). 2006 Jul;65(1):73-8. doi: 10.1157/13090900.
Crigler-Najjar syndrome (CNS) is a very rare disease characterized by severe indirect hyperbilirubinemia from birth with normal liver function. It may cause kernicterus at any age. This disease is due to a total or partial deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the five exons of the ULT1A1 gene.
We reviewed the clinical outcomes of 7 children diagnosed with CNS between 1987 and 2004.
There were three boys and four girls (two of which were homozygote twins). Two children had familial consanguinity. Three out of the six families had another healthy child. The mean follow-up was 8.3 years (14 months-17 years). In all patients, jaundice was detected in the first 3 days of life. The children were admitted to hospital between the fourth and the sixtieth day of life with jaundice and indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients, hemolysis was ruled out and hepatic function was normal. The diagnosis was based on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and on clinical features exclusively in 2 patients. Treatment consisted of phenobarbital and phototherapy from 8 to 16 hours a day in all patients except three. Associated calcium salts were found in 5 patients and cholestyramine was found in two. Two patients developed kernicterus. Two underwent liver transplantation and bilirubin levels became normal. The remaining patients maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological alterations.
Patients with CNS are at greater risk of developing kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl. Phototherapy is very useful in these patients but the only definitive treatment is liver transplantation.
克里格勒 - 纳贾尔综合征（CNS）是一种非常罕见的疾病，其特征为自出生起即出现严重的间接胆红素血症，而肝功能正常。它可在任何年龄导致核黄疸。该疾病是由于ULT1A1基因五个外显子发生突变，导致尿苷二磷酸葡萄糖醛酸基转移酶完全或部分缺乏所致。
我们回顾了1987年至2004年间确诊为CNS的7名儿童的临床结局。
有3名男孩和4名女孩（其中两名是同卵双胞胎）。两名儿童有家族近亲关系。六个家庭中有三个家庭还有另一个健康孩子。平均随访时间为8.3年（14个月至17年）。所有患者在出生后的头3天均检测到黄疸。这些儿童在出生后第4天至第60天因黄疸和间接胆红素水平在12.5至32mg/dl之间而入院。所有患者均排除了溶血，肝功能正常。4例患者的诊断基于基因研究，1例患者基于肝脏中无活性的UGT酶，2例患者仅基于临床特征。除3例患者外，所有患者的治疗均包括苯巴比妥和每天8至16小时的光疗。5例患者发现有相关的钙盐，2例患者发现有考来烯胺。两名患者发生了核黄疸。两名患者接受了肝移植，胆红素水平恢复正常。其余患者的间接胆红素维持在15至25mg/dl之间，无相关神经功能改变。
CNS患者发生核黄疸的风险更高，主要与间接胆红素水平约25mg/dl有关。光疗对这些患者非常有用，但唯一的确定性治疗方法是肝移植。
