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Ophthalmic Genetics Mar 2024Alagille syndrome (AGS) is a genetic disease with multisystemic affection, including ocular manifestations. Recently, a high frequency of posterior segment findings,...
INTRODUCTION
Alagille syndrome (AGS) is a genetic disease with multisystemic affection, including ocular manifestations. Recently, a high frequency of posterior segment findings, including macular changes, has been reported. This publication aims to report an unusual finding of macular atrophy and a focal choroidal excavation in a patient with JAG1 related AGS.
METHODS
Case report.
RESULTS
This publication describes an atypical presentation of focal choroidal excavation (FCE) and unilateral macular atrophy in a 7-year-old male with Alagille syndrome (AGS). Genetic analysis revealed a pathogenic variant in the JAG1 gene. Ophthalmological examination and imaging findings demonstrated characteristic ocular manifestations of AGS, including posterior embryotoxon, chorioretinal atrophy, and thinning of the choroid.
CONCLUSION
The presence of FCE in AGS is uncommon, and the underlying mechanisms remain unclear. Further exploration of similar cases is necessary to better understand the evolution and visual prognosis in patients with AGS and FCE.
PubMed: 38526149
DOI: 10.1080/13816810.2024.2303786 -
Experimental and Clinical... Feb 2024Alagille syndrome is an autosomal-dominantinherited disease characterized by intrahepatic bile duct involvement, congenital heart disease, eye anomalies, skeletal and...
Alagille syndrome is an autosomal-dominantinherited disease characterized by intrahepatic bile duct involvement, congenital heart disease, eye anomalies, skeletal and central nervous system involvement, kidney anomalies, and facial appearance. Liver transplant is the only treatment option for patients with end-stage liver disease and Alagille syndrome. Bilateral peripheral pulmonary artery stenosis is a contraindication for liver transplant due to high mortality, and the decision for liver transplant in patients with bilateral peripheral pulmonary artery stenosis is extremely challenging for anesthesiologists andtransplant surgeons.Wepresent a 2-year-oldfemale patient with successful anesthetic management of a pediatric living donor liver transplant with mild bilateral pulmonary artery stenosis, mild aortic stenosis, and mitral regurgitation due to Alagille syndrome. Anesthesiologists should know the underlying pathophysiological condition and perform a comprehensive preoperative evaluation to determine the correct anesthesia plan in patients with Alagille syndrome who will undergo liver transplants to treat multiple system disorders. Successful perioperative management of Alagille syndrome requires effective communication and collaboration between specialists through a multidisciplinary team approach.
Topics: Humans; Child; Child, Preschool; Alagille Syndrome; Stenosis, Pulmonary Artery; Liver Transplantation; Living Donors; Pulmonary Artery; Anesthesia
PubMed: 38511987
DOI: 10.6002/ect.2023.0308 -
BMJ Case Reports Feb 2024Alagille syndrome (AGS) is a genetic disorder due to mutations in the or genes leading to multisystemic manifestations. Though these patients are at risk of developing...
Alagille syndrome (AGS) is a genetic disorder due to mutations in the or genes leading to multisystemic manifestations. Though these patients are at risk of developing various liver tumours, no cases of hepatoblastoma among young children with cirrhosis in AGS have been reported. We report a male toddler, with cirrhosis due to AGS who developed a hepatoblastoma. He underwent a liver transplant for decompensated chronic liver disease with marked pruritus, very high alpha-fetoprotein levels and malignant liver lesions on positron emission tomography CT. His explant histology revealed a paucity of bile ducts and liver lesions turned out to be hepatoblastoma for which he received postoperative chemotherapy. The genetic testing sent before transplantation confirmed the clinical diagnosis of AGS. Hepatoblastoma should be suspected in any child with AGS presenting with a right upper quadrant mass even in the setting of chronic liver disease.
Topics: Humans; Male; Infant; Child, Preschool; Alagille Syndrome; Hepatoblastoma; Tomography, X-Ray Computed; Liver Neoplasms; Liver Cirrhosis
PubMed: 38417945
DOI: 10.1136/bcr-2022-253080 -
Neuroradiology Feb 2024Alagille syndrome (ALGS) is a multisystem autosomal dominant disorder with highly variable expression. Intracranial arterial and venous anomalies have a reported...
PURPOSE
Alagille syndrome (ALGS) is a multisystem autosomal dominant disorder with highly variable expression. Intracranial arterial and venous anomalies have a reported prevalence of 30-40% and can increase the risk of stroke by 16%. Few reports document the frequency and evolution of cerebrovascular abnormalities (CVAs) in children with ALGS. We aimed to define the spectrum, frequency, and evolution of CVAs in a series of children with ALGS using magnetic resonance angiography (MRA).
METHODS
We conducted a single-center, retrospective study in a large tertiary pediatric hospital. CVAs were grouped into 4 categories: 1) Stenosis or narrowing; 2) Aneurysms and ectasias; 3) Tortuosity; and 4) Vascular anomalies and anatomical variants.
RESULTS
Thirty-two children met the inclusion criteria. The median age at initial diagnosis was 6 (3.8-10.3) years. Thirteen (40%) had follow-up MRI at a mean of 55 (31.5-66) months. Eighteen (56%) had CVAs; the most frequent fell into group 1 (n = 12, 37.5%). CVAs were stable over time, except for one patient with Moyamoya arteriopathy (MMA). One patient developed a transient ischemic attack secondary to an embolic event. Three (9.3%) had microhemorrhages at the initial diagnosis secondary to Tetralogy of Fallot. Another patient had recurrent subdural hematomas of unknown cause.
CONCLUSION
CVAs were stable except in the presence of MMA. Vascular strokes, which are reported in older patients with ALGS, were not a common feature in children under 16 years of age, either at presentation or over the 31.5-66 month follow-up period.
PubMed: 38400955
DOI: 10.1007/s00234-024-03316-z -
Current Pediatric Reviews Feb 2024Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such...
BACKGROUND
Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others.
CASE PRESENTATION
NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found. In the present observation, the cholestasis syndrome with low GGT activity and intense pruritus was the leading symptom of the patient. The examination also revealed other characteristic features of osteo- oto-hepato-enteric syndrome. The patient had facial features that mimicked Alagille syndrome, which complicated the diagnostic search. Moreover, the genetic test revealed two new pathogenic variants in the UNC45A gene.
CONCLUSION
This clinical observation demonstrates the importance of a multidisciplinary approach in the diagnosis of rare genetic diseases and using WES, which can accelerate the diagnosis compared with outdated gene panels.
PubMed: 38375845
DOI: 10.2174/0115733963264010231213103328 -
Annals of Pediatric Cardiology 2023Coronary bifurcation lesions and treatment with two-stent techniques have been developed, including the double kissing (DK) crush technique. The use of this technique in...
Coronary bifurcation lesions and treatment with two-stent techniques have been developed, including the double kissing (DK) crush technique. The use of this technique in children or noncoronary vessels, including pulmonary arteries, has not been described. We present a 12-year-old girl with Alagille syndrome, a ventricular septal defect (VSD), and complex bilateral pulmonary artery (PA) stenoses who is status post six catheterizations for PA angioplasty and stenting to improve her marked right ventricular hypertension. With collaboration between the congenital and structural teams, she successfully underwent the DK crush technique for a complex lesion in her PA. This improved pulmonary flow and allowed for successful surgical VSD closure.
PubMed: 38343512
DOI: 10.4103/apc.apc_60_23 -
Journal of Pediatric Gastroenterology... Mar 2024Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in... (Review)
Review
OBJECTIVE
Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS.
METHODS
We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation.
RESULTS
Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin.
CONCLUSION
Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.
Topics: Humans; Alagille Syndrome; Benzothiepins; Cholestasis; Longitudinal Studies; Pruritus; Clinical Trials as Topic; Infant
PubMed: 38334237
DOI: 10.1002/jpn3.12101 -
Transplantation Proceedings Apr 2024Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT,...
BACKGROUND
Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT, but the adequate dose after pediatric LDLT was unknown. Here, we report micafungin blood concentrations after pediatric LDLT and discuss its safety and adequate dosing.
METHODS
Pediatric patients with data on micafungin concentrations after LDLT were identified. Those with surgical complications were excluded. All patients received standard tacrolimus-based immunosuppression. A micafungin dose of 1 mg/kg was administered once daily for 10 days starting on postoperative day (POD) 1. The trough and peak micafungin blood concentrations were evaluated on PODs 1, 4, 7, and 10. Beta D glucan levels and liver function tests were assessed to determine micafungin effectiveness and safety.
RESULTS
Ten patients were enrolled, with a median age of 1.2 years. The median graft vs body weight ratio was 2.7%. The primary diseases were biliary atresia (n = 7), Alagille syndrome (n = 2), and progressive familial intrahepatic cholestasis type 2 (n = 1). Mean peak micafungin levels were 4.47, 6.27, 5.47, and 5.47 µg/mL on PODs 1, 4, 7, and 10, respectively. Mean trough levels were 2.03, 1.88, and 2.66 µg/mL on PODs 4, 7, and 10, respectively. The micafungin half-lives were 13.7, 14.7, and 14.0 hours on PODs 4, 7, and 10, respectively. Beta D glucan levels were 4.4 pg/mL and 3.7 pg/mL before and after transplantation, respectively, indicating no significant difference (P = .3). No clinical fungal infections were observed.
CONCLUSION
Micafungin administration is safe and effective after pediatric LDLT.
Topics: Humans; Micafungin; Liver Transplantation; Antifungal Agents; Living Donors; Male; Female; Infant; Child, Preschool; Child; Immunosuppressive Agents; Lipopeptides
PubMed: 38326203
DOI: 10.1016/j.transproceed.2024.01.020 -
Journal of Gastroenterology and... May 2024Advances in molecular genetics have uncovered causative genes responsible for neonatal cholestasis. Panel-based next-generation sequencing has been used clinically in...
BACKGROUND AND AIM
Advances in molecular genetics have uncovered causative genes responsible for neonatal cholestasis. Panel-based next-generation sequencing has been used clinically in infants with neonatal cholestasis. We aimed to evaluate the clinical application of single-gene testing and next-generation sequencing and to develop a diagnostic algorithm for neonatal intrahepatic cholestasis.
METHODS
From January 2010 to July 2021, patients suspected of having neonatal intrahepatic cholestasis were tested at the Seoul National University Hospital. If there was a clinically suspected disease, single-gene testing was performed. Alternatively, if it was clinically difficult to differentiate, a neonatal cholestasis gene panel test containing 34 genes was performed.
RESULTS
Of the total 148 patients examined, 49 (33.1%) were received a confirmed genetic diagnosis, including 14 with Alagille syndrome, 14 with neonatal intrahepatic cholestasis caused by citrin deficiency, 7 with Dubin-Johnson syndrome, 5 with arthrogryposis-renal dysfunction-cholestasis syndrome, 5 with progressive familial intrahepatic cholestasis type II, 1 with Rotor syndrome, 1 with Niemann-Pick disease type C, 1 with Kabuki syndrome, and 1 with Phenylalanyl-tRNA synthetase subunit alpha mutation. Sixteen novel pathogenic or likely pathogenic variants of neonatal cholestasis were observed in this study. Based on the clinical characteristics and laboratory findings, we developed a diagnostic algorithm for neonatal intrahepatic cholestasis by integrating single-gene testing and next-generation sequencing.
CONCLUSIONS
Alagille syndrome and neonatal intrahepatic cholestasis caused by citrin deficiency were the most common diseases associated with genetic neonatal cholestasis. Single-gene testing and next-generation sequencing are important and complementary tools for the diagnosis of genetic neonatal cholestasis.
Topics: Humans; Cholestasis, Intrahepatic; High-Throughput Nucleotide Sequencing; Infant, Newborn; Genetic Testing; Algorithms; Male; Female; Alagille Syndrome; Infant
PubMed: 38323732
DOI: 10.1111/jgh.16505 -
Genes & Diseases May 2024
PubMed: 38274370
DOI: 10.1016/j.gendis.2023.04.029