Alagille syndrome misdiagnosed as congenital biliary atresia: a case report and literature review

doi:10.3877/cma.j.issn.2095-3232.2023.06.017

Abstract

Abstract:

Objective

To investigate clinical characteristics, diagnosis, treatment and prognosis of Alagille syndrome (ALGS).

Methods

Clinical data of 1 child with ALGS misdiagnosed as congenital biliary atresia undergoing surgery in the Second Affiliated Hospital of Kunming Medical University in February 2022 were retrospectively analyzed. The boy, aged 10 years and 9 months, was admitted and diagnosed with "congenital biliary atresia" in our hospital in November 2021 due to "repeated yellow skin complicated with itching for more than 10 years and then aggravated for 1 week". Physical examination showed significant developmental disorder, small head circumference, prominent forehead, moderate hypertelorism, pointed chin and limb joint deformity. The liver was tender and palpable 3 cm below the right costal margin. ALT, AST, TB, DB, ALP, GGT levels and other liver function indexes were increased to varying degrees. MRCP showed that intrahepatic bile duct branches were unclear, no dilatation was found and extrahepatic bile ducts were thin. The possibility of specific cholangitis was considered. Ultrasound examination indicated the signs of thin bile ducts and liver injury. ERCP showed linear stenosis of common bile duct and cystic dilatation of common hepatic duct. Relevant studies of pediatric ALGS were searched from Wanfang Data, Chongqing VIP, CNKI, PubMed and MEDLINE and subject to literature review.

Results

On November 25, 2021, the patient underwent biliary stent implantation, and developed severe abdominal pain at postoperative 3 d. The biliary stent was emergently removed and PTCD was performed simultaneously. After multi-disciplinary team consultation, the whole-exome capture for targeted high-throughput sequencing detected c.439C>T (p.Q147*) mutation of JAG1 gene, and heterozygous nonsense mutation in the coding region of JAG1 gene, leading to the change of codon 147 of JAG1 gene from coding glutamine to stop codon. According to JAG1 gene mutation in combination with protruded forehead, two typical manifestations of hypertelorism and chronic cholestasis, the diagnosis of ALGS was confirmed.

Conclusions

ALGS is extremely rare in clinical practice, which is likely to be missed diagnosis and misdiagnosed. Clinical prognosis is relatively poor. With widespread application of genetic testing, more Alagille syndrome patients can be diagnosed accurately. Most patients die of heart disease or severe hepatitis. No effective treatment is available. Symptomatic treatment is mainly adopted. Liver transplantation is probably the optimal procedure.

Key words: Alagille syndrome, Congenital biliary atresia, Diagnosis, Treatment, JAG1 gene

Dingwei Xu, Jiangyun Ma, Xincheng Li, Jie Huang. Alagille syndrome misdiagnosed as congenital biliary atresia: a case report and literature review[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(06): 681-687.

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Figures/Tables 6

References 29

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指标	入院当天	入院3 d	入院1周	参考值
ALT（U/L）	180	172	819	5~40
AST（U/L）	136	107	267	5~80
TB（μmol/L）	19.1	31.0	23.0	3.4~20.5
DB（μmol/L）	8.5	11.4	9.7	0~6.8
IB（μmol/L）	10.6	19.6	13.3	1.7~13.7
TBA（μmol/L）	13.5	24.8	58.4	0~10
ALP（U/L）	470	480	538	<500
GGT（U/L）	203	356	472	11~50
TP（g/L）	75.6	74.6	77.9	64~83
ALB（g/L）	44.3	40.6	45.5	35~50
GLOB（g/L）	31.3	34	32.4	22~33
Cr（μmol/L）	48	46	-	62~115
UA（μmol/L）	383	310	-	208~428
CHOL（mmol/L）	6.94	7.01	7.03	3.49~5.18
TG（mmol/L）	1.7	1.6	1.8	0.25~1.71
WBC（×10⁹/L）	6.7	4.4	-	3.5~9.5
RBC（×10¹²/L）	4.6	10.6	-	3.5~9.5
Hb（g/L）	140	133	-	130~175
Plt（×10⁹/L）	339	334	-	125~350

指标	入院当天	入院3 d	入院1周	参考值
ALT（U/L）	180	172	819	5~40
AST（U/L）	136	107	267	5~80
TB（μmol/L）	19.1	31.0	23.0	3.4~20.5
DB（μmol/L）	8.5	11.4	9.7	0~6.8
IB（μmol/L）	10.6	19.6	13.3	1.7~13.7
TBA（μmol/L）	13.5	24.8	58.4	0~10
ALP（U/L）	470	480	538	<500
GGT（U/L）	203	356	472	11~50
TP（g/L）	75.6	74.6	77.9	64~83
ALB（g/L）	44.3	40.6	45.5	35~50
GLOB（g/L）	31.3	34	32.4	22~33
Cr（μmol/L）	48	46	-	62~115
UA（μmol/L）	383	310	-	208~428
CHOL（mmol/L）	6.94	7.01	7.03	3.49~5.18
TG（mmol/L）	1.7	1.6	1.8	0.25~1.71
WBC（×10⁹/L）	6.7	4.4	-	3.5~9.5
RBC（×10¹²/L）	4.6	10.6	-	3.5~9.5
Hb（g/L）	140	133	-	130~175
Plt（×10⁹/L）	339	334	-	125~350

家族史	胆管稀疏	JAG1突变	临床标准数目^*
无	有	无	3个或更多
无	无	无	4个或更多
无	无	有	1个或更多
有	有	无	1个或更多
有	未知	无	1个或更多
有	无	有	任何1个或更多

家族史	胆管稀疏	JAG1突变	临床标准数目^*
无	有	无	3个或更多
无	无	无	4个或更多
无	无	有	1个或更多
有	有	无	1个或更多
有	未知	无	1个或更多
有	无	有	任何1个或更多

系统/问题	具体描述
肝脏/胆汁淤积	在新生儿期通常表现为高胆红素血症，常伴有白色便
畸形面容	前额宽阔，眼睛深陷，有时可见睑裂上斜、耳廓突出、鼻梁挺直而鼻尖呈蒜头状、尖下巴，上述特点使得脸呈三角形
先天性心脏病	肺动脉狭窄最常见，但也可见肺动脉闭锁、房间隔缺损、室间隔缺损和法洛四联症
中轴骨/椎骨异常	前后位X光片可见蝴蝶椎，偶见半椎体、相邻椎体融合和隐性脊柱裂
眼睛/角膜后胚胎环	前房缺陷，角膜后胚胎环（虹膜与角膜交界处突起的Schwalbe氏环）最常见

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