Alagille Syndrome- This is an inherited medical condition usually found in children. Disease causes progressive loss of bile ducts within the liver leading to excessive accumulation of bile in the liver. The liver abnormalities result in numerous medical complications, including cirrhosis of the liver. In this article, we will discuss in detail about the various causes, symptoms, and treatment for Alagille Syndrome.
How Is Alagille Syndrome Defined?
- Genetic Disorder- Genetic mutation is autosomal dominant disorder.1
- Prevalence- Prevalence of the syndrome is 1:100,000 live births.
- Age- Alagille syndrome is often observed in infants and children.
- Organs Affected- The syndrome is a genetic disorder of liver, kidney, heart, eyes and spine.
- Characteristics- Facial appearance is characteristics of the disease.
- Liver Failure- Liver disease may end up in liver failure in 15% of the cases.
- Bile Duct- Children affected with Alagille syndrome tend to have lost their bile ducts within the first year of their life. Narrowing of the bile ducts outside the liver results in excessive accumulation of bile in liver. The excessive bile spills over normal liver cells and causes cell damage and fibrosis, which results in cirrhosis of the liver.
- Renal Dysplasia- Renal abnormalities may be associated with facial characteristics and liver abnormalities.2
Causes Of Alagille Syndrome
- Genetic mutation of gene JAGGED1 results in Alagille syndrome.1
- Gene mutation is inherited from one of the parents.
Narrowing of Bile Duct-
- Alagille Syndrome as stated is a genetic pathologic condition causing narrowing and malformation of the bile ducts.
- Obstruction of bile flow caused by intra and extra hepatic stenosis causes accumulation of bile in liver. Bile spill in liver causes severe liver damage.
- Over time, there is scarring of liver, which prevents normal liver function.
- Liver is unable to discard the waste products from the blood.
Symptoms Of Alagille Syndrome
Non-Specific Symptoms Of Alagille Syndrome:
Specific Symptoms Of Alagille Syndrome:
- Facial Features-
- Broad forehead
- Prominent forehead
- Deep-set eyes
- Small pointed chin.
- Liver Disease-
- Skin- Yellowish discoloration
- Yellow- Sclera and Conjunctive
- Pale Stool
- Tetralogy of Fallot
- Pulmonary stenosis
- Overriding aorta
- Ventricular septal defect
- Right ventricular hypertrophy
- Kidney Disease
- Central Nervous System
- Bleeding may results in stroke
- Fatty deposits in the skin (xanthomas) 1
Diagnosis of Alagille Syndrome
- Liver Biopsy-
- Reduced flow of bile in liver and to intestine is confirmed by liver biopsy and endoscopy. Biopsy shows bile duct stenosis and less number of bile duct in biopsy tissue.
- Biopsy shows biliary atresia.
- Echocardiography and Electrocardiography-
- Cardiologist evaluates presence of a congenital heart disease.
- X-ray of Vertebral Column-
- Bone defect in vertebral column is seen in X-ray. Diagnostic finding is butterfly shape of one or more of the vertebral bones of the spinal column.
- X-Ray of hip joint and femoral bone shows bilateral Osteochondrosis of the femoral heads similar to Perthes Disease.4
- Genetic Testing-
- Confirms the diagnosis.
Treatment For Alagille Syndrome
- Ursodeoxycholic Acid5, Cholestyramine-
- Prescribed for Itching caused by the buildup of bile in the blood and skin.
- Prescribed for Pruritus
- Anticholesterol Medications-
- Elevated cholesterol
- Treatment for xanthomas
- Absorption of fat is reduced because of absence of bile.
- MCT oil helps to absorb fat in intestine.
- Supplement vitamin A, D, E and K.
- Bile deficiency in intestine causes inadequate absorption of Vitamin A, D, K and E.
- Vitamin A Therapy- for night blindness and red eyes.
- Vitamin D Therapy- Osteoporosis and bone weakness
- Liver Transplant-
- Recommended for Cirrhosis of liver.
- Cardiac Surgery-
- Fallot of tetralogy
- Repair of Pulmonary artery stenosis
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Vajro P1, Ferrante L, Paolella G.
Clin Res Hepatol Gastroenterol. 2012 Jun;36(3):275-7.
2. Renal anomalies in Alagille syndrome: a disease-defining feature.
Kamath BM1, Podkameni G, Hutchinson AL, Leonard LD, Gerfen J, Krantz ID, Piccoli DA, Spinner NB, Loomes KM, Meyers K.
Am J Med Genet A. 2012 Jan;158A(1):85-9. doi: 10.1002/ajmg.a.34369. Epub 2011 Nov 21.
3. Alagille syndrome and other hereditary causes of cholestasis.
Hartley JL1, Gissen P, Kelly DA.
Clin Liver Dis. 2013 May;17(2):279-300.
4. Perthes-like disease in Alagille syndrome.
Massobrio M1, Antonietti G, Necci F, Esposito C.
J Pediatr Orthop B. 2011 Sep;20(5):299-302.
5. Management of cholestatic pruritus in paediatric patients with alagille syndrome: the King's College Hospital experience.
Kronsten V1, Fitzpatrick E, Baker A.
J Pediatr Gastroenterol Nutr. 2013 Aug;57(2):149-54. doi: 10.1097/MPG.0b013e318297e384.