Commentary, Jldt Vol: 10 Issue: 3
Amrutha Dasgupta *
Department of endoscopy, SRM University, Chennai, Tamilnadu, India.
*Corresponding author: Amrutha D, Department of endoscopy, SRM Medical College, Chennai, Tamil nadu, India.
Received date: 11 May, 2021; Accepted date: 26 May, 2021; Published date: 29 May, 2021.
Citation: Dasgupta A (2021). Alagille Syndrome 2021, 10:2(196)
Alagille syndrome (AS) is an autosomal dominant disorder (OMIM 118450) associated with malfunctions of the liver, heart, skeleton, eye, and kidneys and a attributes facial appearance. . Mutations/deletions in 2 genes related with the Notch signaling alleyways are known to cause ALGS: JAGGED1 (encoding the Notch signaling pathway ligand JAGGED1) in 89% of ALGS cases; and NOTCH2 (encrypting one of the Notch receptors) in a small minority of ALGS cases
In patients with ALGS, disarrange Notch signaling is related with the abnormal development of the intrahepatic bile ducts. Although mutations causing ALGS have now been discovered, diagnostic challenges remain because there are no genotype-phenotype associations. Improved understanding of the biology and natural history of disease is required to design new therapies and assess their efficacy
Some individuals may have lenient forms of the disorder while others may have more serious forms. Common symptoms, which often evolve during the first three months of life, include obstruction of the flow of bile from the liver (cholestasis), yellowing of the skin and mucous membranes (jaundice), deficient weight gain and growth, and severe itching (pruritis).
Because of decreased number of bile ducts, individuals with alagille syndrome can develop jaundice and cholestasis usually throughout the first four months of life. Cholestasis refers to decreased or obstructed flow of bile from the liver
ALGS is a multisystem disorder with a wide spectrum of clinical flexibility ranging from life-threatening liver or cardiac disease to only subclinical demonstrations, such as mildly abnormal liver enzymes, a heart murmur, butterfly vertebrae, posterior embryotoxic, or typical facial features
In the majority of cases, individuals with ALGS present in early childhood with cholestasis (conjugated hyperbilirubinemia with high GGT, increased serum bile acids, and raised cholesterol and triglycerides), which manifest as jaundice, intense pruritus, xanthomas (fatty accumulation on the extensor surfaces), and failure to thrive due to fat assimilation
Due to the inconstant clinical presentation of Alagille syndrome, it is difficult to know the exact occurrence and prevalence. Chronic cholestasis transpires in a very high proportion of cases, and most frequently, presents in the neonatal period or first 3 months of life, with jaundice due to associated hyperbilirubinaemi. Posterior embryotoxic, the most regular ophthalmic feature of ALGS, has been announced in up to 90% of patients
This is prominence of the halfway positioned Schwalbe's ring (or line) at the point where the corneal endothelium and the uveal trabecular meshwork joint
A typical form of segmentation anomaly known as ‘butterfly' vertebrae (Figure 2) may arise in at least 80% of cases This consists of a sagittal cleft in one or more thoracic vertebrae, detectable on antero-posterior radiograph, and is due to failure of fusion of the anterior vertebral arches
Vertebral segmentation peculiarly occur in a wide range of disorders22 but, with the irregularity of deletion 22q11 syndrome (again), the relatively symmetrical ‘butterfly' advent is unusual. The cases usually present with unstable liver function test (Increased total and direct bilirubin), escalated bile acid concentration in the serum, generalized pruritus, xanthomas and rarely retarded growth
Recently, there is a growing consensus that liver biopsy is not mandatory if clinic-biochemical affirmation of cholestasis along with other characteristic manifestations of Alagillle syndrome are present
Alagille syndrome (ALGS) is usually a cholestatic liver disorder affecting multiple systems such as heart, eyes, face, kidneys, central nervous system and skeletal system
In view of the complexity in presentation and multi-organ involvement, management of cases with Alagille syndrome should be done by the combined effort of a multidisciplinary team, comprising of medical geneticists, gastroenterologists, hepatologists, nutritionist, cardiologists, ophthalmologists, nephrologists, liver transplantation, and if necessary, a neurosurgeon for better long-term outcome