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Alagille Syndrome: About Two Cases and Literature Review Asian Journal of Pediatric Research 4(3): 1-6, 2020; Article no.AJPR.59593 ISSN: 2582-2950 Alagille Syndrome: About Two Cases and Literature Review M. Akhrif1*, A. Radi1, M. Kmari1, A. Ourrai1, A. Hassani1, R. Abilkassem1 1 and A. Agadr 1Department of Pediatric, Mohamed V Military Training Hospital, Rabat, Morocco. Authors’ contributions This work was carried out in collaboration among all authors. Authors MA and AR designed the study, performed the statistical analysis, wrote the protocol and wrote the first draft of the manuscript. Authors MA and AR managed the analyses of the study. Author MA managed the literature searches. All authors read and approved the final manuscript. Article Information DOI: 10.9734/AJPR/2020/v4i330148 Editor(s): (1) Dr. Thomaz Rafael Gollop, Universidade de Sao Paulo, Brazil. Reviewers: (1) Boris Luis Garcia Freire, Havana University, Cuba. (2) Ana Cristina Ruiz Peña, University of Zaragoza, Spain. Complete Peer review History: http://www.sdiarticle4.com/review-history/59593 Received 05 June 2020 Accepted 10 August 2020 Case Study Published 22 August 2020 ABSTRACT Alagille syndrome is a multi-systemc genetic disorder with variable phenotypic penetrance that was first described in 1969 by Daniel Alagille.It is characterized by anomalies of the intrahepatic bile ducts, heart, eye and skeleton, which are associated with facial features . The prognosis depends on the severity of the liver and heart diseases. The authors reported two cases characterized by the variability of clinical expression and evolution. The study concerned two girls aged of 2 and 4 months with no family history, who developed cholestatic jaundice evolving from the first month of life. The aim of this work is to remind the different clinical expressivity and the differentmodalities to manage the patients in order to ensure a best quality of life. Keywords: Alagille syndrome; cholestatic jaundice; clinical expressivity; genetic disorder. 1. INTRODUCTION Incidence of Alagille Syndrome (ALGS) is 1/100,000 live births. Transmission follows an Alagille syndrome (ALGS) is a multisystemc autosomal dominant pattern, with a high degree disorder with variable phenotypic penetrance. of penetrance but variable expressivity [1]. A _____________________________________________________________________________________________________ *Corresponding author: Email: [email protected]; Akhrif et al.; AJPR, 4(3): 1-6, 2020; Article no.AJPR.59593 more rare autosomal recessive pattern has also Abdominal ultrasound was normal. been described . The gene defect in 60 to 75% of Ophthalmological examination revealed posterior cases is an intragenic (94%) mutation in the JAG embryotoxon in both eyes. Cardiac evaluation 1 gene located on chromosome 20p12 or demonstrated thymic hypertrophy and systolic deletion JAG1 mutations are found in one third of acceleration of the flow at the passage of the patients presenting with only one or two clinical pulmonary bifurcation suggestive of branch features of Alagille syndrome. Mutations in the stenosis probably in the process of formation to gene encoding NOTCH 2 have been described be documented by angio-scanner: compatible as well [2]. Initial diagnosis was based with an alagille syndrome, with in addition a on the presence of intrahepatic bile duct continuous flow suggestive of a permeable paucity and at least 3 other clinical features: arterial canal. The patient received appropriate Chronic cholestasis, cardiac disease, ocular correction of vitamin deficiences : Vitamin K, abnormalities, skeleton abnormalities, and Vitamin D. Vitamin A and vitamin E. characteristic facial features. 3.2 Case Number 2. MATERIALS AND METHODS A 4-month-old girl, hospitalised 40 days We report the case of two girls aged of 2 and 4 later for prolonged jaundice related to months with no family history, who developed Escherichia coli urinary tract infection cholestatic jaundice evolving from the first month (Hepatobiliary ultrasound was normal), a of life. We have consulted several references, to persistence of cutaneous mucous enrich the discussion and address the subject in jaundice, with intermittent discoloured its different approaches. This manuscript allowed stools and dark urine. No pruritus or us to review the clinical and biological hemorrhagic syndrome. The general manifestations of this syndrome. It has allowed review found an infant in good general us to has also made it possible to judge the condition, apyretic, icteric on a pink quality of the initial care of these sick. background, tonic, reactive. Facies doesn't find obvious dysmorphia outside of a A literature review has enriched this work with bandbag forehead. Psychomotor the aim of understanding the diversity of this development was normal. Abdomen's soft, pathology and the advances in genetic research, there was not hepato splenomegaly. in particularin Alagille syndrome. Cardiopulmonary auscultation was normal. Neurological exam was normal. The rest of 3. CASE REPORT the somatic examination was unremarkable. Laboratory examination 3.1 Case Number results were as follow : Hepatic cholestasis: Total Bilirubin: 99 mg/l, Direct Infant 2 months old, third of 3 siblings, with no Bilirubin: 74mg/l.: gamma- family history, who developed since the 4th day glutamyltranspeptidase 1500 IU/l(N: 5-32 of life cutaneous-mucosal jaundice of U/L). Hepatic cytolysis: aspartate progressive aggravation with colored urine and aminotransferase: 411 IU/l(N: 15-55 U/L) , pale yellow stools without other associated signs. alanine aminotransferase: 375 IU/l. (N: 5- The general review found apyretic infant, Icteric 45 U/L).Reduced prothrombin: on a pale background, dysmorphic fasciae: 58%.Serologies of syphilitic, bulging forehead, implanted low ears, toxoplasmosis, rubella, HIVand Hepatitis hypertelorism, sunken eyes and pointed chin. B,C were negative. He has no The rest of the clinical examination was hydroelectrolytic disturbance, kidney unremarkable. Laboratory examination results function was normal. Serum total protein were as follow: Hepatic cytolysis : aspartate and albumin were normal. Alpha aminotransferase : 193 (N: 15-55 U/L); alanine Foetoprotein: 550 ng/ml, Ferritin: 400. aminotransferase: 152 (N: 5-45 U/L),. Hepatic TSH: 2.97µUI/ml, CBEU: sterile. Amino cholestasis: alkaline phosphatase : 719(N: 145- acid chromatography in the blood: normal. 420 U/L); gamma-glutamyltranspeptidase: 1711, Amino acid chromatography in urine: total bilirubin 103mg/dL, conjugated bilirubin: normal. Amoniemia: 194 g/dlµ (N :31-123). 79mg/dL . TSH: 2.44 (normal). Cervico dorso Abdominal ultrasound was normal, the lumbar rachis X-ray revealed Butterfly wing main bile duct was not dilated. Direct vertebrae pathognomonic for alagille syndrome. radiography of the vertebral column 2 Akhrif et al.; AJPR, 4(3): 1-6, 2020; Article no.AJPR.59593 revealed non pathologic signs.Bili MRI Survival to 6 years is decreased to 40% appearance that may be compatible with compared with 95% in patients without type IV extrahepatic biliary atresia. intracardiac disease. The exact mechanism of Anapathic account of the liver biopsy disease remains unknown and there is no concludes to a morphological aspect of a correlation between the genetic mutation in Cholestase liver secondary to intra-hepatic JAG1 and the presence or type of cardiovascular ductular paucity (ductopenia). disease [4]. One of our patients have systolic Ophthalmologic examination revealed an acceleration of the flow at the passage of the incomplete embryontoxon. Cardiac pulmonary bifurcation suggestive of branch evaluation demonstrated hypoplasia of the stenosis, the other one have hypoplasia of the pulmonary bronchi. On the symptomatic pulmonary bronchi. therapeutic level , the patient has been put on : Vitamin K. Vitamin D , Vitamin A and vitamin E. 4. DISCUSSION Alagille syndrome is a multisystemic disorder involving predominately the liver, heart, skeleton, eyes, and face. The diagnosis of Alagille syndrome is traditionally based on bile duct paucity in association with at least 3 of 5 major clinical features: chronic cholestasis; cardiac defect; skeletal abnormalities; ocular abnormalities and characteristic facial features. Several mechanisms which may cause paucity of intrahepatic bile ducts. One mechanism may be the poor development of intrahepatic arterial branches. Expansion of the portal vein mesenchyma( PVM) also appears to be dependent on JAG1 signaling: Jagged1 in the Fig. 1. Cervico dorso lumbar rachis X-ray portal vein mesenchyma (PVM) regulates revealed Butterfly wing vertebrae intrahepatic bile duct development and controls pathognomonic for alagille syndrome the formation of the second layer of the ductal plate, allowing the biliary epithelial cells (BECs) Systemic vascular anomalies of the aorta (both to eventually remodel into a lumenized duct [1]. aneurysmand coarctation), renal, celiac, superior mesenteric, and subclavian arteries have all Alagille based his original definition of bile duct been reported [5]. There is no genotype- paucity as a bile duct to portal tract ratio less phenotype correlation, so the exact mechanism than 0.5, one of our patients, the second one, of the development of these vascular has bile duct paucity. More recent reports found abnormalities remains unknown. The expression cholestasis in only 89% of patients and bile duct of JAG1 in all major arteries, however, has been paucity in 75%. both of our patients have established in studies of human embryos [6]. It cholestasis. has been proposed that vasculopathy
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