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Bilateral manifestations of xerophthalmia. a Right eye – the cornea is opaque and covered by an amniotic membrane. b Left eye – conjunctival irritation and corneal opacification.
Source publication
To report the occurrence of xerophthalmia and keratomalacia in a patient with Alagille syndrome.
The patient's record and relevant literature were reviewed.
A 3-year-old boy with Alagille syndrome was examined at our institution due to severe bilateral ocular irritation. A corneal ulcer and keratomalacia were found in the right eye and severe dryne...
Context in source publication
Context 1
... Staphylococcus mitis. The patient was treated with intensive topical cefamezine, garamycin and lubrication, and experienced a gradual improvement. Three weeks after his initial presentation to our clinic, the corneal infiltrate resolved, but a marked thinning remained. He underwent amniotic membrane transplantation with lower punctual occlusion ( fig. 2). Due to the clinical findings and his systemic condition, a suspicion of vitamin A deficiency was raised. This was confirmed by serum analysis of vitamin A, which measured 2 µg/dl; this is significantly DOI: 10.1159/000357642 © 2013 S. Karger AG, Basel ...Similar publications
Notch is a cell-cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton...
Background
paucity of interlobular bile ducts is an important observation at liver biopsy in the diagnostic work-up of neonatal cholestasis. To date, other than in the Alagille syndrome, syndromic paucity of interlobular bile ducts has been documented in four cholestatic neonates with HFN1β mutations. A syndromic phenotype, known as renal cysts and...
Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by developmental abnormalities in several organs including the liver, heart, eyes, vertebrae, kidneys, and face. The majority (90-94 %) of ALGS cases are caused by mutations in the JAG1 (JAGGED1) gene, and in a small percent of patients (∼1 %) mutations in the NOTCH2 gene have...
Alagille syndrome is a rare autosomal dominant disorder characterized by chronic cholestasis due to paucity of intrahepatic biliary ducts, characteristic facies, peripheral pulmonary stenosis, ocular posterior embryotoxon and skeletal abnormalities. Very little information is available on the cholestatic, lipid and lipoprotein profiles in individua...
Pediatric hepatocellular carcinoma (HCC) is the second common malignant liver tumor in children after hepatoblastoma. It differs from the adult HCC in the etiological predisposition, biological behavior and lower frequency of cirrhosis. Perinatally acquired hepatitis-B virus, hepatorenal tyrosinemia, progressive familial intrahepatic cholestasis, g...
Citations
... Vitamin A deficiency is estimated to occur in up to two thirds of patients with cirrhosis. 11 In comparison, less than 1% of the US population are estimated at risk for vitamin A deficiency. 75 Prevalence is higher among patients with poor dietary intake and those living in endemic areas, women, alcoholics, patients with cholestatic liver diseases (eg, primary biliary cholangitis [PBC], cystic fibrosis-related liver disease, and Alagille syndrome), and advanced or decompensated cirrhosis (Child-Pugh class C). 11,21,[76][77][78][79][80] In liver failure, elevated total bilirubin and higher body mass index are predictors of profound vitamin A deficiency. 11 Epidemiologic, clinical, and diagnostic information regarding deficiency of vitamin A are listed in table 1. ...
Malnutrition is prevalent in cirrhosis. Vitamin and mineral deficiencies, including vitamin D, vitamin A, and zinc, are common and have been shown to correlate with survival. Our aim was to review the mechanisms of vitamin D, vitamin A, and zinc deficiencies in cirrhosis and the clinical assessment of affected patients, their outcomes based on the current literature, and management. This is a narrative review including the relevant literature for cirrhosis and vitamin D, vitamin A, and zinc deficiencies. Vitamin D deficiency has important effects in cirrhosis, regardless of the cause of chronic liver disease.These effects include associations with fibrosis and outcomes such as infections, hepatocellular carcinoma, and mortality. Vitamin A deficiency is associated with liver disease progression to cirrhosis and clinical decompensation, including occurrence of ascites or hepatic encephalopathy. Zinc deficiency can lead to hepatic encephalopathy and impaired immune function. Such deficiencies correlate with patient survival and disease severity. Caution should be applied when replacing vitamin D, vitamin A, and zinc to avoid toxicity. Identification and appropriate treatment of vitamin and mineral deficiencies in cirrhosis may reduce specific nutritional and cirrhosis-related adverse events. Routine monitoring of vitamin A, vitamin D and zinc levels in cirrhosis should be considered.
Hepatic disease in Alagille syndrome manifests with a wide range of clinical severity, even in patients with the same genetic mutation. Liver disease commonly presents in the neonatal period during evaluation for cholestasis with elevated bilirubin and GGT. The classic finding on liver biopsy is bile duct paucity; however, this is not diagnostic and not all children with Alagille syndrome have paucity on liver biopsy. There are specific clinical criteria for diagnosis of Alagille syndrome, including bile duct paucity on liver biopsy; however with the availability of genetic testing, not all criteria have to be met for the diagnosis in a patient with known genetic mutation or positive family history. In contrast to some other pediatric liver disorders, ALGS liver disease can improve over the first several years of life. Despite this, in some children cholestasis can progress to end-stage liver disease, cirrhosis, portal hypertension, and eventual need for liver transplantation. There is no specific treatment for hepatic disease in Alagille syndrome, and management focuses on treatment of symptoms of chronic cholestasis, including pruritus, xanthomata, malnutrition, and fat-soluble vitamin deficiencies. Surgical therapies, such as external biliary diversion, are used in children when medical management of cholestasis fails, although these procedures are not effective in all children. Ultimately if liver disease progresses to cirrhosis and complications of portal hypertension, liver transplant may be indicated.
Many pediatric gastrointestinal disorders have ophthalmic manifestations. The detection of these ophthalmic features may help establish the underlying diagnosis. Pediatric liver, intestinal and pancreatic diseases with ophthalmic manifestations are discussed with extensive review of the relevant literature. Where relevant the pathologic mechanisms underlying these manifestations are discussed.
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.
