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Archivos Argentinos de Pediatria Apr 2018Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal...
INTRODUCTION
Alagille syndrome (AS) is a cholestatic disease secondary to scarcity of interlobular bile ducts. It is associated with extrahepatic manifestations, and renal involvement is frequent.
OBJECTIVES
To describe the prevalence, type and outcome of renal pathology in children with AS.
PATIENTS AND METHODS
The presence and outcome of renal pathology was retrospectively studied in 21 children who met AS criteria.
RESULTS
Renal pathology was observed in 18 patients (85.7%): (1) ultrasound variations in 7 patients (6 cases of bilateral renal dysplasia and 1 case of renal agenesis); (2) distal renal tubular acidosis in 2 patients; (3) a drop in glomerular filtration and/or proteinuria in 16 patients. The frequency of a drop in glomerular filtration was similar between patients with and without pathological kidney ultrasound findings.
CONCLUSIONS
Our study confirms a high prevalence of renal involvement, which enhances the importance of diagnosis and renal function follow-up in children with AS.
Topics: Adolescent; Alagille Syndrome; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Kidney Diseases; Male; Prevalence; Prognosis; Retrospective Studies; Young Adult
PubMed: 29557611
DOI: 10.5546/aap.2018.eng.149 -
Global Spine Journal Sep 2019Systematic review (Level 4). (Review)
Review
STUDY DESIGN
Systematic review (Level 4).
OBJECTIVE
To summarize the demographics, clinical presentations, and conditions associated with butterfly vertebrae.
METHODS
A systematic search was performed of multiple databases. A total of 279 articles were identified for screening. Case series or case reports of butterfly vertebrae with adequate clinical detail were complied.
RESULTS
Eighty-two total articles (109 patients) were selected for final inclusion. Sixty-one percent of patients presented with a single butterfly vertebra, while 39% were multiple. The most common location for butterfly vertebrae was T1. Fifty-six percent of cases were associated with a syndrome, the most common being spondylocostal dysostosis. The presence of multiple butterfly vertebra was strongly associated with a syndrome or additional anomalies ( < .001). Overall, the most common presenting complaint was low back pain. Seventy percent of patients had associated spinal disease. Other organ systems affected included musculoskeletal (43%), craniofacial (30%), neurologic (27%), cardiovascular (24%), genitourinary (23%), gastrointestinal (22%), laboratory abnormality (16%), and endocrine (9%).
CONCLUSIONS
This study is the largest collection of butterfly vertebrae cases to date. Butterfly vertebrae are associated with spinal deformity and multiple butterfly vertebrae may indicate a syndromic illness. Low back pain or disc herniation may occur with lumbar butterfly vertebrae however the etiology of this phenomena has not been rigorously explained. Many diseases and syndromes are associated with butterfly vertebrae.
PubMed: 31448202
DOI: 10.1177/2192568218801016 -
American Journal of Ophthalmology Case... Dec 2021We describe the ocular findings in a patient with Alagille syndrome, included those obtained with ultra-widefield and anterior-segment optical coherence tomography...
PURPOSE
We describe the ocular findings in a patient with Alagille syndrome, included those obtained with ultra-widefield and anterior-segment optical coherence tomography (AS-OCT) imaging.
OBSERVATIONS
A previously asymptomatic 29-year-old woman with a heterozygous pathogenic variant in the gene was referred for an ophthalmic evaluation. The ocular abnormalities included bilateral posterior embryotoxon, iris atrophy, retinal pigmentary changes in the peripheral and peripapillary regions, and optic disc elevation. Ultra-widefield OCT showed bilateral retinal thinning with increased choroidal hyperreflectivity in the areas of peripheral retinopathy and optic disc elevation. AS-OCT confirmed bilateral iris atrophy.
CONCLUSIONS AND IMPORTANCE
The ocular abnormalities observed in the present case represent clinical features characteristic of Alagille syndrome. Both ultra-widefield and AS-OCT were useful for assessing the ocular abnormalities in Alagille syndrome.
PubMed: 34632159
DOI: 10.1016/j.ajoc.2021.101213 -
Journal of Cardiology Cases Jan 2020Alagille syndrome (ALGS) is characterized by cholestasis due to paucity of intrahepatic bile ducts, cardiac anomalies, ophthalmologic abnormalities, skeletal...
BACKGROUND
Alagille syndrome (ALGS) is characterized by cholestasis due to paucity of intrahepatic bile ducts, cardiac anomalies, ophthalmologic abnormalities, skeletal abnormalities, and characteristic facies. Mid-aortic syndrome (MAS) is a rare entity characterized by segmental narrowing of the proximal abdominal aorta and ostial stenosis of its major branches. We report a case of ALGS with MAS involving severe renal artery stenosis (RAS).
CASE
A four-year-old Japanese boy was referred to our hospital because of cholestatic liver dysfunction. He was diagnosed with ALGS due to having all five characteristic hallmarks. He had high blood pressure (152/84 mmHg) at his first visit. 3D-CT angiography showed coarctation of the abdominal aortic trunk, severe ostial stenosis of the celiac artery, superior mesenteric artery, and bilateral RAs. He was diagnosed with MAS, and treated with metoprolol, cilnidipine, and aspirin.
DISCUSSIONS
While vascular abnormalities are reported to occur in 9% of ALGS patients, MAS with ALGS was only reported in 11 patients between 1951 and 2011. In Japan, there were no reports of ALGS coexisting with MAS with the exception of one case with RAS. In addition to the vessels of the heart, it is important to examine patients with ALGS for abnormalities of other vessels.< Mid-aortic syndrome (MAS) is a rare entity characterized by segmental narrowing of the proximal abdominal aorta and ostial stenosis of its major branches. While MAS is a very rare complication in case of Alagille syndrome (ALGS), it results in significant morbidity and mortality. Thus, surveillance for vascular abnormalities not only in the heart but also other vessels is important in ALGS.>.
PubMed: 31933703
DOI: 10.1016/j.jccase.2019.09.010 -
Annals of Transplantation Oct 2020BACKGROUND Alagille syndrome (AGS) is an autosomal dominant hereditary disorder characterized by identifiable abnormalities in the liver, heart, face, skeleton, and...
BACKGROUND Alagille syndrome (AGS) is an autosomal dominant hereditary disorder characterized by identifiable abnormalities in the liver, heart, face, skeleton, and eyes. Recently, liver transplantation (LT) has been proposed as a therapeutic strategy for patients with AGS complicated by end-stage liver disease, but clinical experience in performing anesthesia in LT for AGS is still scarce. We aimed to summarize our preliminary experience in the anesthetic management of LT for AGS in this study. MATERIAL AND METHODS We reviewed the cases of 11 patients with AGS who underwent LT from September 2017 to April 2019. Preoperative multi-system comorbidities, intraoperative details, and postoperative outcomes were retrospectively collected and summarized. RESULTS Cardiopulmonary abnormalities were common (81.8%) in AGS patients before LT, and the most frequent comorbidity was pulmonary artery stenosis. After careful anesthetic evaluation and perioperative management, all patients survived during the perioperative period without significant cardiovascular complications. However, there was an unexpectedly high prevalence of surgical complications and re-operations in AGS patients compared to biliary atresia recipients (54.5% vs. 22.4%, P=0.031; and 45.5% vs. 15.3%, P=0.028, respectively). CONCLUSIONS Perioperative management of LT for AGS patients can be particularly challenging, requiring a full understanding of the pathophysiology, as well as a careful preoperative evaluation of the multi-system comorbidities. The high prevalence of postoperative surgical complications should be a matter of concern.
Topics: Alagille Syndrome; Anesthetics; Child; Child, Preschool; End Stage Liver Disease; Female; Humans; Infant; Liver Transplantation; Male; Retrospective Studies; Severity of Illness Index
PubMed: 33046687
DOI: 10.12659/AOT.924282 -
The Journal of Extra-corporeal... Dec 2022Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but...
Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but may not be limited to the liver, heart, musculoskeletal, skin, and the eyes. The most common congenital heart defect associated with Alagille syndrome is multilevel right ventricular outflow tract obstruction with multiple central and peripheral branch pulmonary arterial stenoses occurring in up to two-thirds of these patients. We report two cases of Alagille syndrome who underwent extensive pulmonary arterial branch rehabilitation and experienced unusual oxygenator failure during cardiopulmonary bypass (CPB). We present lessons learned from these two cases and the changes that we implemented in our practice that facilitated smooth conduct of CPB in other cases that we performed subsequently.
Topics: Humans; Alagille Syndrome; Cardiopulmonary Bypass; Hypertension, Pulmonary; Heart Defects, Congenital; Oxygenators
PubMed: 36742021
DOI: 10.1182/ject-2200022 -
Pharmacological Research Jan 2024Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have... (Review)
Review
Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.
Topics: Female; Pregnancy; Humans; Alagille Syndrome; Cholestasis, Intrahepatic; Ursodeoxycholic Acid; Pregnancy Complications
PubMed: 38000562
DOI: 10.1016/j.phrs.2023.107006 -
Hypertension (Dallas, Tex. : 1979) Sep 2021Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of... (Review)
Review
Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.
Topics: Alagille Syndrome; Aortic Dissection; Atherosclerosis; Fibromuscular Dysplasia; Humans; Hypertension, Renovascular; Neurofibromatosis 1; Renal Artery Obstruction; Takayasu Arteritis
PubMed: 34455817
DOI: 10.1161/HYPERTENSIONAHA.121.17004 -
Journal of the American Heart... Mar 2022Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for...
Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and "extensive" interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient-specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention-induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long-segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.
Topics: Alagille Syndrome; Constriction, Pathologic; Humans; Pulmonary Artery; Stenosis, Pulmonary Artery; Stroke
PubMed: 35253446
DOI: 10.1161/JAHA.121.023532 -
Liver International : Official Journal... Aug 2020Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children... (Review)
Review
Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children and are associated with impaired bile flow (ie cholestasis), pruritus and potentially fatal liver disease. There are no effective or approved pharmacologic treatments for these diseases (standard medical treatments are supportive only), and new, noninvasive options would be valuable. Typically, bile acids undergo biliary secretion and intestinal reabsorption (ie enterohepatic circulation). However, in these diseases, disrupted secretion of bile acids leads to their accumulation in the liver, which is thought to underlie pruritus and liver-damaging inflammation. One approach to reducing pathologic bile acid accumulation in the body is surgical biliary diversion, which interrupts the enterohepatic circulation (eg by diverting bile acids to an external stoma). These procedures can normalize serum bile acids, reduce pruritus and liver injury and improve quality of life. A novel, nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT), a key molecule in the enterohepatic circulation that reabsorbs bile acids from the intestine. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of paediatric cholestatic liver diseases. This review explores the rationale of inhibition of the IBAT as a therapeutic target, describes IBAT inhibitors in development and summarizes the current data on interrupting the enterohepatic circulation as treatment for cholestatic liver diseases including ALGS and PFIC.
Topics: Alagille Syndrome; Bile Acids and Salts; Carrier Proteins; Child; Cholestasis; Cholestasis, Intrahepatic; Humans; Infant; Membrane Glycoproteins; Quality of Life
PubMed: 32492754
DOI: 10.1111/liv.14553