What are the clinical features of ARPKD?
ARPKD, an inherited disorder that affects 1 in 20,000 live births, is an important cause of chronic kidney disease in children. The disease commonly presents in neonates; in some individuals it is diagnosed later in life but is rarely diagnosed in adults. Typically, the severity of the kidney and hepatic manifestations is inversely correlated and depends on the age at diagnosis. ARPKD is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene and is characterized by massively enlarged cystic kidneys, hepatic fibrosis, and pulmonary hypoplasia secondary to oligohydramnios, which may lead to respiratory insufficiency and death in one-third of affected newborns. Although siblings may suffer from ARPKD, the disease does not occur in their parents. More than half of the patients are detected during late pregnancy, and those who are undetected on prenatal evaluation usually survive the perinatal period.
The liver disease consists of enlargement and fibrosis of portal areas, bile duct proliferation, and hypoplasia of portal vein branches leading to portal hypertension; some patients have nonobstructive intrahepatic bile duct dilatation (Caroli disease). A minority of affected individuals can present for the first time as older children or adolescents, usually with manifestations of portal hypertension as a result of congenital hepatic fibrosis (CHF) (gastrointestinal bleeding from varices, hepatosplenomegaly, or hypersplenism) or episodes of cholangitis resulting from Caroli disease. ARPKD is rarely diagnosed in adults. Genetic testing for ARPKD is available, with a mutation detection rate of approximately 95%. All reported associated gene mutations are archived in the ARPKD mutation public database.
