Curious Case of Alagille Syndrome: Case Report with NANDANIC-NOC Linkage in Care Plan

Alagille syndrome is a rare and complex multisystem disorder caused by an autosomal dominant genetic mutation of JAG1 (90% cases) and NOTCH2 (1-2% cases) genes located on the short arm of chromosome 20. This case is reported as per the CARE (for Case Reports, 2013) guidelines. A 14-year old male, known case of chronic cholestatic liver disease of neonatal onset, diagnosed with Alagille syndrome as evident from NOTCH 2 mutation in genetic analysis and paucity of intrahepatic bile ducts on biopsy presented with portal hypertension, growth failure and persistent hyperbilirubinemia.

A case of Alagille syndrome presenting with chronic cholestasis in an adult

Alagille syndrome (AGS) is a complex multisystem disorder that involves mainly the liver, heart, eyes, face, and skeleton. The main associated clinical features are chronic cholestasis due to a paucity of intrahepatic bile ducts, congenital heart disease primarily affecting pulmonary arteries, vertebral abnormalities, ocular embryotoxon, and peculiar facies. The manifestations generally become evident at a pediatric age. AGS is caused by defects in the Notch signaling pathway due to mutations in JAG1 or NOTCH2. It is inherited in an autosomal dominant pattern with a high degree of penetrance, but variable expressivity results in a wide range of clinical features. Here we report on a 31-year-old male patient who presented with elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase, and was diagnosed with AGS associated with the JAG1 mutation after a comprehensive workup.

Clinical features and JAGI gene analysis of 2 cases with Alagille syndrome / 中华实用儿科临床杂志

Objective To carry out the detection of JAGI gene in children with chronic cholestasis and to im-prove the diagnostic level and understanding of Alagille syndrome. Methods Two cases of chronic cholestasis with multiple organ involvement were selected as the research subjects and their clinical data,laboratory test results were col-lected. Two milliliter peripheral intravenous heparin anticoagulan blood was drawn from each patient. All fragments of 26 exons of the JAGI gene were amplified by polymerase chain reaction - sequence based on typing method. Results One patient with chronic cholestasis,heart murmur and dysmorphic face showed bile duct paucity in liver biopsy and a novel heterozygous mutation c. 809 809delG(p. G270Dfs*142)in 6 exon. Abnormal amino acid replaced JAG1 protein and resulted in truncation of the JAG1 protein. The part of epidermal growth factor(EGF)like repeats region loss and the cysteine rich region completely lost. One case with typical chronic cholestasis and dysmorphic face showed a known IVS20 - 2 5delTAAG heterozygous mutation which resulted in splice site changes. Conclusion A novel JAGI gene mutation c. 809 809delG(p. G270Dfs*142)is helpful to screen JAGI gene of Notch signal transduction pathway for chronic cholestasis with multiple organs involvement in children.

Omega-3 Polyunsaturated Fatty Acid for Cholestasis due to Bile Duct Paucity / 대한소아소화기영양학회지

Omega (omega)-3 polyunsaturated fatty acids appear to be effective in preventing and treating parenteral nutrition-associated liver disease, and several mechanisms were proposed for this observation. An 8-week-old male infant with cholestasis and acholic stool was diagnosed non-syndromic intrahepatic interlobular bile duct paucity by open-wedge liver biopsy. Initially he was treated with usual supportive medical therapy, including ursodeoxycholic acid. However, the clinical status and laboratory tests did not improve. Omega (omega)-3 polyunsaturated fatty acids (initially intravenous administration and oral administration later), were started and his liver function, including aminotransferase level and bilirubin levels normalized, and the ivory stool color turned green. We report the possible effectiveness of omega-3 polyunsaturated fatty acids as a potent choleretic agent for non-syndromic intrahepatic interlobular bile duct paucity, a very rare structural pediatric hepatic disease.

A Case of Nonsyndromic Intrahepatic Bile Duct Paucity with Congenital Bilateral Vocal Cord Paralysis and 13q Deletion / 대한소아소화기영양학회지

Nonsyndromic intrahepatic bile duct paucity is known to be associated with several kinds of etiology such as infection, chromosomal anomaly, metabolic disease and idiopathic. We report a rare case of intrahepatic bile duct paucity with congenital bilateral vocal cord paralysis and 13q deletion.

Clinical Evaluation of Syndromic and Nonsyndromic Intrahepatic Bile Duct Paucity / 대한소아소화기영양학회지

PURPOSE: The aims of this study were to evaluate the clinical manifestations and prognosis of the syndromic and nonsyndromic intrahepatic bile duct paucity (IHBDP). METHODS: We studied histology of 42 infants with neonatal cholestasis. Fourteen patients were diagnosed as IHBDP. We evaluated the clinical manifestations, courses and prognosis retrospectively. RESULTS: Underlying disease of the 42 infants with neonatal cholestasis were biliary atresia in 23, intrahepatic bile duct paucity in 14 (Alagille syndrome in 4 and nonsyndromic IHBDP in 10), neonatal hepatitis in 5 infants. The mean ratio of the bile ducts per portal tract was 0.087 (range: 0~0.5). The manifestations in 4 patients with Alagille syndrome demonstrated as follows: characteristic face in 3, chronic cholestasis in 4, posterior embryotoxon in 2, vertebral anomalies in 2, peripheral pulmonary stenosis in 2. One of 4 patients of Alagille syndrome improved cholestasis and the other 3 patients were remained their cholestasis and growth retardation. All patients of the nonsyndromic IHBDP were idiopathic. Seven out of 8 patients of nonsyndromic IHBDP showed improvement of cholestasis, and one patient received liver transplantation due to cirrhosis. CONCLUSION: This study suggested that IHBDP should be considered in the differential diagnosis of neonatal cholestasis. The outcome of idiopathic IHBDP was better than predicted.