We retrospectively studied the records of 6 Malaysian children who were diagnosed with Alagille Syndrome (AGS) according to this criteria from January 1999 to January 2001, at the Institute of Paediatrics, Kuala Lumpur Hospital. Four patients (66%) had a positive family history. Thirteen individuals (6 patients and 7 relatives) were diagnosed with AGS in these 5 families. Only 6/13 (46%) of them presented with liver involvement. All 6 patients presented with typical facies and cholestasis (100%). Three (50%) presented with portal hypertension (PHT) with synthetic liver dysfunction (1 died), 1/6 (17%) have PHT and normal synthetic liver function. Two have cleared their jaundice but have biochemical evidence of hepatitis and hepatomegaly, four have congenital heart disease 5/6 posterior embryotoxon, 2/6 butterfly vertebrae, 4/6 hyperlipidaemia and 4/6 failure to thrive. One patient has a Jagged-1 gene disruption at the translocation breakpoint locus 20p12.3 2n = 46,XX,t(12.20) (q22, p12.3). 5/6 (83%) are still alive. Two-thirds of our patients developed chronic liver disease by 3 years of age. Two-thirds of the index patients have a family history. Only 46% of individuals in these families have clinical evidence of liver involvement. Mortality depends on cardiac/renal disease, end-stage liver failure and intercurrent infection.
Alagille Syndrome/complications ; Alagille Syndrome/genetics ; Alagille Syndrome/*physiopathology ; Malaysia

No abstract available.
Alagille Syndrome* ; Cholestasis ; Xanthomatosis*

Alagille Syndrome ; Humans

Alagille syndrome (ALGS), also known as arteriohepatic dysplasia, is an autosomal dominant disease with multisystem involvement. In this disease, the Notch signalling pathway is impaired due to mutation in JAG1 (ALGS type 1) or NOTCH2 (ALGS type 2) gene, affecting multiple organs or systems such as liver, heart, eyes, vertebrate and face. The main clinical features of ALGS include chronic cholestasis, congenital heart disease, mild vertebral segmentation abnormalities, characteristic face, postcorneal embryotoxon and poor kidney development. This article reviews the recent advances in the pathogenesis, clinical presentations, diagnosis and treatment of this syndrome.
Alagille Syndrome ; diagnosis ; etiology ; therapy ; Humans

Alagille Syndrome ; diagnosis ; pathology ; Child ; Humans ; Liver ; pathology ; Male

Alagille Syndrome ; pathology ; Child, Preschool ; China ; Female ; Humans ; Infant ; Male

Cholestasis results from impairment in the excretion of bile, which may be due to mechanical obstruction of bile flow or impairment of excretion of bile components into the bile canaliculus. When present, cholestasis warrants prompt diagnosis and treatment. The differential diagnosis of cholestasis beyond the neonatal period is broad and includes congenital and acquired etiologies. It is imperative that the clinician differentiates between intrahepatic and extrahepatic origin of cholestasis. Treatment may be supportive or curative and depends on the etiology. Recent literature shows that optimal nutritional and medical support also plays an integral role in the management of pediatric patients with chronic cholestasis. This review will provide a broad overview of the pathophysiology, diagnostic approach, and management of cholestasis beyond the neonatal and infancy periods.
Alagille Syndrome ; Bile ; Bile Canaliculi ; Cholelithiasis ; Cholestasis* ; Diagnosis ; Diagnosis, Differential ; Hepatitis ; Hepatolenticular Degeneration ; Humans ; Jaundice ; Pruritus

PURPOSE: Alagille syndrome is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged1(JAG1) gene, which encodes a ligand of Notch, has been found mutated in Alagille syndrome. The aim of the study was to investigate the mutation analysis of JAG1 gene in Korean patients with Alagille syndrome. METHODS: Genomic DNA was extracted from peripheral leukocytes of 6 patients. The 26 exons of JAG1 gene were amplified and PCR products were directly sequenced. RESULTS: Two novel frameshift mutations were found. 118delC in exon 2 was found in a patient who developed hepatocellular carcinoma at 4 years of age. 999-1000delTG was identified in exon 7. CONCLUSION: Mutations identified in this study are expected to give rise to truncated proteins.
Alagille Syndrome* ; Carcinoma, Hepatocellular ; DNA ; Exons ; Frameshift Mutation ; Heart ; Humans ; Leukocytes ; Liver ; Polymerase Chain Reaction ; Spine

PURPOSE: Infants with Alagille syndrome (AGS) are occasionally misdiagnosed as biliary atresia and subsequently undergo Kasai operation. The purpose of this study was to investigate the outcome of patients with AGS who had previously received Kasai operation during infancy. METHODS: This retrospective study was conducted at the Department of Pediatrics, Samsung Medical Center. We compared the prognosis and mortality between those who had undergone Kasai operation during infancy (Kasai group) and those who had not (non-Kasai group). RESULTS: Among the 15 children with AGS, five had received Kasai operation, while 10 had not. All subjects in the Kasai group revealed neonatal cholestasis, while 70% of the non-Kasai group showed neonatal cholestasis. Liver transplantation was performed in 100% (5/5) among the Kasai group, and 20.0% (2/10) among the non-Kasai group (p=0.007). Mortality was observed in 60.0% (3/5) among the Kasai group, and 10.0% (1/10) among the non-Kasai group (p=0.077). CONCLUSION: Although overall mortality rate did not significantly differ between the two groups, the proportion of patients receiving liver transplantation was significantly higher in the non-Kasai group. The relatively worse outcome in AGS patients who had received Kasai operation may be due to the unfavorable influences of Kasai operation on the clinical course of AGS, or maybe due to neonatal cholestasis, irrespective of the Kasai operation.
Alagille Syndrome* ; Biliary Atresia ; Child ; Cholestasis ; Humans ; Infant ; Liver Transplantation ; Mortality ; Pediatrics ; Prognosis ; Retrospective Studies

Alagille syndrome (ALGS) is an autosomal dominant disorder which is mainly caused by JAG1 gene mutation and can affect multiple systems including the liver, heart, eyes, skeleton and face. This paper reports the clinical and genetic features of an ALGS patient. A 2-year-and-9-month-old boy was referred to the hospital with the complaint of abnormal liver function and heart murmur discovered over two years. Jaundice of the skin and sclera was not observed. The child had a prominent forehead, left esotropia, depressed nasal bridge and micromandible. The two lungs were clear on auscultation, but a systolic cardiac murmur of grade 2/6 could be heard between the 2nd and 3rd intercostal space at the left sternal border. Neither abdominal distension nor enlarged liver or spleen was discovered. X-ray radiography uncovered butterfly malformation of the 6th and 8th thoracic vertebrae. Serum biochemistry analysis revealed elevation of total bile acids, bilirubin and transaminases. Based on the clinical characteristics and the consultation opinion of the ophthalmologist, the child was diagnosed to have ALGS with Duane retraction syndrome. DNA direct sequencing detected a novel JAG1 mutation c.2419delG(p.Glu807AsnfsX819) in the child. Symptomatic and supportive therapy was performed thereafter and clinical follow-up was conducted until he was 4 years and 2 months. In the follow-up visits, his general condition remained stable, but the facial malformations, left esotropia, cardiac murmur and abnormal liver function persistend. The long-term outcome needed to be observed.
Alagille Syndrome ; genetics ; therapy ; Child, Preschool ; Humans ; Jagged-1 Protein ; genetics ; Male ; Mutation