Author information

¹Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. bruno.ranchin@chu-lyon.fr.

²Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.

³Faculté de Médecine Lyon Est, Université de Lyon, Lyon, France.

⁴Service d'Hépato-gastroentérologie pédiatrique, Centre de Référence de l'atrésie des voies biliaires et des cholestases génétiques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.

⁵INSERM, UMR 1033, Faculté de Médecine Lyon Est, Université de Lyon, Lyon, France.

Abstract

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disease with a high interindividual variability. The two causative genes JAG1 and NOTCH2 are expressed during kidney development, can be reactivated during adulthood kidney disease, and Notch signalling is essential for vascular morphogenesis and remodelling in mice. Liver disease is the most frequent and severe involvement; neonatal cholestasis occurs in 85% of cases, pruritus in 74%, xanthomas in 24% of cases, and the cumulative incidences of portal hypertension and liver transplantation are 66% and 50% respectively at 18 years of age. Stenosis/hypoplasia of the branch pulmonary arteries is the most frequent vascular abnormality reported in ALGS. Kidney involvement is present in 38% of patients, and can reveal the disease. Congenital anomalies of the kidney and urinary tract is reported in 22% of patients, hyperchloremic acidosis in 9%, and glomerulopathy and/or proteinuria in 6%. A decreased glomerular filtration rate is reported in 10% of patients and is more frequent after liver transplantation for ALGS than for biliary atresia. Kidney failure has been frequently reported in childhood and adulthood. Renal artery stenosis and mid aortic syndrome have also frequently been reported, often associated with hypertension and stenosis and/or aneurysm of other large arteries. ALGS patients require kidney assessment at diagnosis, long-term monitoring of kidney function and early detection of vascular complications, notably if they have undergone liver transplantation, to prevent progression of chronic kidney disease and vascular complications, which account for 15% of deaths at a median age of 2.2 years in the most recent series.