小儿肝豆状核变性37例

Hepatolenticular Degeneration in 37 Children

目的分析小儿肝豆状核变性(WD)的临床特点。方法按照WD诊断标准,对37例(男24例,女13例;年龄2～13岁)以不同器官损害为首发症状的WD患儿的临床特点、实验室检查及影像学检查、误诊情况和治疗及预后作回顾性分析。结果首发症状以肝功能受损为主者33例,以神经系统受累为主者3例,同时以肝病和神经系统为主者1例。有明确家族史者2例。6例误诊患儿中误诊为肠梗阻1例,胆石症、肾炎各2例,腹泻病1例。检查角膜K-F环37例,阳性3例。实验室检查ALT>40 U/L者32例,24 h尿铜>100μg/24 h 37例,清蛋白<40 g/L 21例,铜蓝蛋白<0.2 g/L 37例。9例血氨>45μmol/L,尿气相色谱质谱(GC-MS)分析在肝损害患儿中可见乳酸和半乳糖醇,在肾损害患者中可见多种氨基酸。肝损害严重时血浆串联质谱分析可见多种氨基酸水平升高。腹部超声检查提示肝脾大26例,肝脏CT检查密度异常3例,头颅CT或MRI检查信号异常4例。行肝脏穿刺活组织检查提示慢性肝炎并结节性肝硬化1例。37例患儿予低铜饮食,青霉胺驱铜及葡萄糖酸锌治疗,32例明显好转,4例死亡,1例放弃治疗。结论WD临床表现复杂多样,易被误诊。血氨、GC-MS和血浆串联质谱分析可作为反映病情的指标之一。

Objective To analyze the clinical characteristics of children with hepatolenticular degeneration （WD）. Methods The first onset symptoms of various organ dysfuncion in 37 children with WD were reviewed. Their clinical feature,laboratory examination,imaging examination and therapy were analyzed. Results The first onset symptoms in 33 cases were manifestations of the liver problems and in 3 ca- ses manifestated central nervous system problems, and 1 case manifestated both liver and CNS problems. Two cases had clear family history. A- mong 6 misdiagnosed cases, 1 case was misdiagnosed as intestinal obstruction,2 cases cholelithiasis,2 cases nephritis, and 1 case diarrhoea. Three had positive cornea K - F ring. All patients had increased urinary copper excretions higher than 100 μg/24 hours and ceruloplasmin de- creased（ 〈0.2 g/L） ,32 cases had increased ALT （ 〉 40 U/L） ,21 cases had decreased albumin（ 〈 40 g/L）. Children＇s severe liver dys- function, blood ammonia increased,and 9 patients had increased blood ammonia（ 〉 45μmoL/L）. Lactic acid and galactitol in patients detec- ted by gas chromatography - mass spectrometry suggested liver injury and multiple amino acids in renal dysfunction. Multiple amino acids de- tected by electrospray ionization tandem mass spectrum were in severe liver injury. Hepatomegaly or splenomegaly were detected by abdominal ultrasound in 26 cases. Density anomaly on liver CT were found in 3 cases. Abnormal signal on brain CT or MRI were found in 4 cases. Liver biopsy showed chronic hepatitis and hepatic cirrhosis in 1 case. The results of treatment with low copper diet,D - penicillamine and zinc sul- phate in 37 cases were that 32 patients became better,4 cases died and 1 case gave up treatment. Conclusions The clinical characteristics are diverse,which leads to the higher misdiagnosis rate. Further understanding of hepatolenticular degeneration is helpful to the early clinic diagnosis and therapy. Blood ammonia,urine organic acid and plasma amino acid would be the index for the condition of the illness.